bluuebunny/crossref_metadata_2025_split huggingface dataset:
Radical transformation pathway towards sustainable electricity via evolutionary steps
Authors: Bogdanov Dmitrii , Farfan Javier , Sadovskaia Kristina , Aghahosseini Arman , Child Michael , Gulagi Ashish , Oyewo Ayobami Solomon , de Souza Noel Simas Barbosa Larissa , Breyer Christian 
Published: March 2019

AbstractA transition towards long-term sustainability in global energy systems based on renewable energy resources can mitigate several growing threats to human society simultaneously: greenhouse gas emissions, human-induced climate deviations, and the exceeding of critical planetary boundaries. However, the optimal structure of future systems and potential transition pathways are still open questions. This research describes a global, 100% renewable electricity system, which can be achieved by 2050, and the steps required to enable a realistic transition that prevents societal disruption. Modelling results show that a carbon neutral electricity system can be built in all regions of the world in an economically feasible manner. This radical transformation will require steady but evolutionary changes for the next 35 years, and will lead to sustainable and affordable power supply globally.
Resource sharing in technologically defined social networks
Authors: Shirado Hirokazu , Iosifidis George , Tassiulas Leandros , Christakis Nicholas A. 
Published: March 2019

AbstractTechnologically enabled sharing-economy networks are changing the way humans trade and collaborate. Here, using a novel ‘Wi-Fi sharing’ game, we explored determinants of human sharing strategy. Subjects (N = 1,950) participated in a networked game in which they could choose how to allocate a limited, but personally not usable, resource (representing unused Wi-Fi bandwidth) to immediate network neighbors. We first embeddedN = 600 subjects into 30 networks, experimentally manipulating the range over which subjects could connect. We find that denser networks decrease any wealth inequality, but that this effect saturates. Individuals’ benefit is shaped by their network position, with having many partners who in turn have few partners being especially beneficial. We propose a new, simplified “sharing centrality” metric for quantifying this. Further experiments (N = 1,200) confirm the robustness of the effect of network structure on sharing behavior. Our findings suggest the possibility of interventions to help more evenly distribute shared resources over networks.
Rapid active zone remodeling consolidates presynaptic potentiation
Authors: Böhme Mathias A. , McCarthy Anthony W. , Grasskamp Andreas T. , Beuschel Christine B. , Goel Pragya , Jusyte Meida , Laber Desiree , Huang Sheng , Rey Ulises , Petzoldt Astrid G. , Lehmann Martin , Göttfert Fabian , Haghighi Pejmun , Hell Stefan W. , Owald David , Dickman Dion , Sigrist Stephan J. , Walter Alexander M. 
Published: March 2019

AbstractNeuronal communication across synapses relies on neurotransmitter release from presynaptic active zones (AZs) followed by postsynaptic transmitter detection. Synaptic plasticity homeostatically maintains functionality during perturbations and enables memory formation. Postsynaptic plasticity targets neurotransmitter receptors, but presynaptic mechanisms regulating the neurotransmitter release apparatus remain largely enigmatic. By studying Drosophila neuromuscular junctions (NMJs) we show that AZs consist of nano-modular release sites and identify a molecular sequence that adds modules within minutes of inducing homeostatic plasticity. This requires cognate transport machinery and specific AZ-scaffolding proteins. Structural remodeling is not required for immediate potentiation of neurotransmitter release, but necessary to sustain potentiation over longer timescales. Finally, mutations in Unc13 disrupting homeostatic plasticity at the NMJ also impair short-term memory when central neurons are targeted, suggesting that both plasticity mechanisms utilize Unc13. Together, while immediate synaptic potentiation capitalizes on available material, it triggers the coincident incorporation of modular release sites to consolidate synaptic potentiation.
Genetic dissection of Nodal and Bmp signalling requirements during primordial germ cell development in mouse
Authors: Senft Anna D. , Bikoff Elizabeth K. , Robertson Elizabeth J. , Costello Ita 
Published: March 2019

AbstractThe essential roles played by Nodal and Bmp signalling during early mouse development have been extensively documented. Here we use conditional deletion strategies to investigate functional contributions made by Nodal, Bmp and Smad downstream effectors during primordial germ cell (PGC) development. We demonstrate that Nodal and its target gene Eomes provide early instructions during formation of the PGC lineage. We discover that Smad2 inactivation in the visceral endoderm results in increased numbers of PGCs due to an expansion of the PGC niche. Smad1 is required for specification, whereas in contrast Smad4 controls the maintenance and migration of PGCs. Additionally we find that beside Blimp1, down-regulated phospho-Smad159 levels also distinguishes PGCs from their somatic neighbours so that emerging PGCs become refractory to Bmp signalling that otherwise promotes mesodermal development in the posterior epiblast. Thus balanced Nodal/Bmp signalling cues regulate germ cell versus somatic cell fate decisions in the early posterior epiblast.
Znhit1 controls intestinal stem cell maintenance by regulating H2A.Z incorporation
Authors: Zhao Bing , Chen Ying , Jiang Ning , Yang Li , Sun Shenfei , Zhang Yan , Wen Zengqi , Ray Lorraine , Liu Han , Hou Guoli , Lin Xinhua 
Published: March 2019

AbstractLgr5+ stem cells are crucial to gut epithelium homeostasis; however, how these cells are maintained is not fully understood. Zinc finger HIT-type containing 1 (Znhit1) is an evolutionarily conserved subunit of the SRCAP chromosome remodeling complex. Currently, the function of Znhit1 in vivo and its working mechanism in the SRCAP complex are unknown. Here we show that deletion of Znhit1 in intestinal epithelium depletes Lgr5+ stem cells thus disrupts intestinal homeostasis postnatal establishment and maintenance. Mechanistically, Znhit1 incorporates histone variant H2A.Z into TSS region of genes involved in Lgr5+ stem cell fate determination, including Lgr5, Tgfb1 and Tgfbr2, for subsequent transcriptional regulation. Importantly, Znhit1 promotes the interaction between H2A.Z and YL1 (H2A.Z chaperone) by controlling YL1 phosphorylation. These results demonstrate that Znhit1/H2A.Z is essential for Lgr5+ stem cell maintenance and intestinal homeostasis. Our findings identified a dominant role of Znhit1/H2A.Z in controlling mammalian organ development and tissue homeostasis in vivo.
Unlocking the potential of weberite-type metal fluorides in electrochemical energy storage
Authors: Euchner Holger , Clemens Oliver , Reddy M. Anji 
Published: March 2019

AbstractSodium-ion batteries (NIBs) are a front-runner among the alternative battery technologies suggested for substituting the state-of-the-art lithium-ion batteries (LIBs). The specific energy of Na-ion batteries is significantly lower than that of LIBs, which is mainly due to the lower operating potentials and higher molecular weight of sodium insertion cathode materials. To compete with the high energy density of LIBs, high voltage cathode materials are required for NIBs. Here we report a theoretical investigation on weberite-type sodium metal fluorides (SMFs), a new class of high voltage and high energy density materials which are so far unexplored as cathode materials for NIBs. The weberite structure type is highly favorable for sodium-containing transition metal fluorides, with a large variety of transition metal combinations (M, M’) adopting the corresponding Na2MM’F7 structure. A series of known and hypothetical compounds with weberite-type structure were computationally investigated to evaluate their potential as cathode materials for NIBs. Weberite-type SMFs show two-dimensional pathways for Na+ diffusion with surprisingly low activation barriers. The high energy density combined with low diffusion barriers for Na+ makes this type of compounds promising candidates for cathode materials in NIBs.
Orbital magneto-optical response of periodic insulators from first principles
Authors: Lebedeva Irina V. , Strubbe David A. , Tokatly Ilya V. , Rubio Angel 
Published: March 2019

AbstractMagneto-optical response, i.e. optical response in the presence of a magnetic field, is commonly used for characterization of materials and in optical communications. However, quantum mechanical description of electric and magnetic fields in crystals is not straightforward as the position operator is ill defined. We present a reformulation of the density matrix perturbation theory for time-dependent electromagnetic fields under periodic boundary conditions, which allows us to treat the orbital magneto-optical response of solids at the ab initio level. The efficiency of the computational scheme proposed is comparable to standard linear-response calculations of absorption spectra and the results of tests for molecules and solids agree with the available experimental data. A clear signature of the valley Zeeman effect is revealed in the continuum magneto-optical spectrum of a single layer of hexagonal boron nitride. The present formalism opens the path towards the study of magneto-optical effects in strongly driven low-dimensional systems.
The gravity dependence of pharmacodynamics: the integration of lidocaine into membranes in microgravity
Authors: Kohn Florian P. M. , Hauslage Jens 
Published: March 2019

AbstractTo realize long-term manned space missions, e.g. to Mars, some important questions about pharmacology under conditions of different gravity will have to be answered to ensure safe usage of pharmaceuticals. Experiments on the International Space Station showed that the pharmacokinetics of drugs are changed in microgravity. On Earth, it is well known that the incorporation of substances into cellular membranes depends on membrane fluidity, therefore the finding that membrane fluidity is gravity dependent possibly has effects on pharmacodynamics of hydrophobic and amphiphilic substances in microgravity. To validate a possible effect of gravity on pharmacodynamics, experiments have been carried out to investigate the incorporation of lidocaine into plain lipid membranes under microgravity conditions. In microgravity, the induced increase in membrane fluidity associated with lidocaine incorporation is smaller compared to 1g controls. This experiment concerning the gravity dependence of pharmacodynamics in real microgravity clearly shows that the incorporation of amphipathic drugs into membranes is changed in microgravity. This might have significant impact on the pharmacology of drugs during long-term space missions and has to be investigated in more detail to be able to assess possible risks.
Continuous targeted kinase inhibitors treatment induces upregulation of PD-L1 in resistant NSCLC
Authors: Jiang Li , Guo Fuchun , Liu Xiaoke , Li Xiaoyu , Qin Qing , Shu Pei , Li Yi , Wang Yongsheng 
Published: March 2019

AbstractFirst-generation epidermal growth factor receptor (EGFR) targeted kinase inhibitors (TKIs) are still used in selected non-small cell lung cancer (NSCLC) patients despite the resistance. Based on the correlation of programmed cell death receptor ligand 1 (PD-L1) and EGFR signaling pathway, whether continuous TKIs treatment will affect PD-L1 expression after disease progression remains unclear. To investigate the potential change of PD-L1 expression in TKI-resistant NSCLC after continuous TKIs treatment, we treated H1975 and HCC827 for more than one month and explored the possible effect on immune cells as well as underlying biological mechanisms. We found that continuous exposure to TKIs induced upregulation of PD-L1 in H1975 and HCC827. Moreover, PD-L1 upregulation significantly inhibited proliferation and slightly promoted apoptosis of T cells. We observed the activation of STAT3 and ERK1/2 along with the PD-L1 upregulation. With the pathway inhibitors, we found ERK1/2 pathway involved in inducing PD-L1 in resistant lung cancer. This study provides preclinical evidence that continuous TKIs treatment may induce PD-L1 expression in resistant NSCLC, resulting in the suppression of T cell function and immune escape. ERK1/2 pathway inhibitors, PD-L1/PD-1 inhibitors or combination strategies should be considered to reverse the resistance to TKIs in NSCLC patients.
Grasping movements toward seen and handheld objects
Authors: Camponogara Ivan , Volcic Robert 
Published: March 2019

AbstractGrasping movements are typically performed toward visually sensed objects. However, planning and execution of grasping movements can be supported also by haptic information when we grasp objects held in the other hand. In the present study we investigated this sensorimotor integration process by comparing grasping movements towards objects sensed through visual, haptic or visuo-haptic signals. When movements were based on haptic information only, hand preshaping was initiated earlier, the digits closed on the object more slowly, and the final phase was more cautious compared to movements based on only visual information. Importantly, the simultaneous availability of vision and haptics led to faster movements and to an overall decrease of the grip aperture. Our findings also show that each modality contributes to a different extent in different phases of the movement, with haptics being more crucial in the initial phases and vision being more important for the final on-line control. Thus, vision and haptics can be flexibly combined to optimize the execution of grasping movement.
Prevention of EloR/KhpA heterodimerization by introduction of site-specific amino acid substitutions renders the essential elongasome protein PBP2b redundant in Streptococcus pneumoniae
Authors: Winther Anja Ruud , Kjos Morten , Stamsås Gro Anita , Håvarstein Leiv Sigve , Straume Daniel 
Published: March 2019

AbstractThe RNA binding proteins EloR and KhpA are important components of the regulatory network that controls and coordinates cell elongation and division in S. pneumoniae. Loss of either protein reduces cell length, and makes the essential elongasome proteins PBP2b and RodA dispensable. It has been shown previously in formaldehyde crosslinking experiments that EloR co-precipitates with KhpA, indicating that they form a complex in vivo. In the present study, we used 3D modeling and site directed mutagenesis in combination with protein crosslinking to further study the relationship between EloR and KhpA. Protein-protein interaction studies demonstrated that KhpA forms homodimers and that KhpA in addition binds to the KH-II domain of EloR. Site directed mutagenesis identified isoleucine 61 (I61) as crucial for KhpA homodimerization. When substituting I61 with phenylalanine, KhpA lost the ability to homodimerize, while it still interacted clearly with EloR. In contrast, both homo- and heterodimerization were lost when I61 was substituted with tyrosine. By expressing these KhpA versions in S. pneumoniae, we were able to show that disruption of EloR/KhpA heterodimerization makes the elongasome redundant in S. pneumoniae. Of note, loss of KhpA homodimerization did not give rise to this phenotype, demonstrating that the EloR/KhpA complex is crucial for regulating the activity of the elongasome. In support of this conclusion, we found that localization of KhpA to the pneumococcal mid-cell region depends on its interaction with EloR. Furthermore, we found that the EloR/KhpA complex co-localizes with FtsZ throughout the cell cycle.
Climate change drives trait-shifts in coral reef communities
Authors: Kubicek Andreas , Breckling Broder , Hoegh-Guldberg Ove , Reuter Hauke 
Published: March 2019

AbstractClimate change is expected to have profound, partly unforeseeable effects on the composition of functional traits of complex ecosystems, such as coral reefs, and some ecosystem properties are at risk of disappearing. This study applies a novel spatially explicit, individual-based model to explore three critical life history traits of corals: heat tolerance, competitiveness and growth performance under various environmental settings. Building upon these findings, we test the adaptation potential required by a coral community in order to not only survive but also retain its diversity by the end of this century under different IPCC climate scenarios. Even under the most favourable IPCC scenario (Representative Concentration Pathway, RCP 2.6), model results indicate that shifts in the trait space are likely and coral communities will mainly consist of small numbers of temperature-tolerant and fast-growing species. Species composition of coral communities is likely to be determined by heat tolerance, with competitiveness most likely playing a subordinate role. To sustain ~15% of current coral cover under a 2 °C temperature increase by the end of the century (RCP 4.5), coral systems would have to accommodate temperature increases of 0.1–0.15 °C per decade, assuming that periodic extreme thermal events occurred every 8 years. These required adaptation rates are unprecedented and unlikely, given corals’ life-history characteristics.
Characterization, mechanism of action and optimization of activity of a novel peptide-peptoid hybrid against bacterial pathogens involved in canine skin infections
Authors: Greco Ines , Emborg Agnete Plahn , Jana Bimal , Molchanova Natalia , Oddo Alberto , Damborg Peter , Guardabassi Luca , Hansen Paul R. 
Published: March 2019

AbstractIntegumentary infections like pyoderma represent the main reason for antimicrobial prescription in dogs. Staphylococcus pseudintermedius and Pseudomonas aeruginosa are frequently identified in these infections, and both bacteria are challenging to combat due to resistance. To avoid use of important human antibiotics for treatment of animal infections there is a pressing need for novel narrow-spectrum antimicrobial agents in veterinary medicine. Herein, we characterize the in vitro activity of the novel peptide-peptoid hybrid B1 against canine isolates of S. pseudintermedius and P. aeruginosa. B1 showed potent minimum inhibitory concentrations (MICs) against canine S. pseudintermedius and P. aeruginosa isolates as well rapid killing kinetics. B1 was found to disrupt the membrane integrity and affect cell-wall synthesis in methicillin-resistant S. pseudintermedius (MRSP). We generated 28 analogues of B1, showing comparable haemolysis and MICs against MRSP and P. aeruginosa. The most active analogues (23, 26) and B1 were tested against a collection of clinical isolates from canine, of which only B1 showed potent activity. Our best compound 26, displayed activity against P. aeruginosa and S. pseudintermedius, but not the closely related S. aureus. This work shows that design of target-specific veterinary antimicrobial agents is possible, even species within a genus, and deserves further exploration.
Early overnutrition reduces Pdx1 expression and induces β cell failure in Swiss Webster mice
Authors: Glavas Maria M. , Hui Queenie , Tudurí Eva , Erener Suheda , Kasteel Naomi L. , Johnson James D. , Kieffer Timothy J. 
Published: March 2019

AbstractChildhood obesity and early rapid growth increase the risk for type 2 diabetes. Such early overnutrition can be modeled in mice by reducing litter size. We investigated the effects of early overnutrition and increased dietary fat intake on β cell function in Swiss Webster mice. On a moderate-fat diet, early overnutrition accelerated weight gain and induced hyperinsulinemia in pups. Early overnutrition males exhibited higher β cell mass but reduced islet insulin content and Pdx1 expression. Males had a high diabetes incidence that was increased by early overnutrition, characterized by a progressive increase in insulin secretion as well as β cell death, indicated by histological analysis and increased circulating miR-375 levels. Females maintained normoglycemia throughout life. High-fat diet (HFD) increased diabetes incidence in males, whereas low-fat diet was completely protective. This protective effect was abolished in early overnutrition males transiently exposed to HFD in early life. Although Swiss Webster mice are not known to be diabetes-prone, the high diabetes incidence suggests an underlying genetic susceptibility that can be induced by overnutrition and increased dietary fat intake in early life. Thus, the nutritional environment in early life may impact long-term β cell function and increase diabetes risk, particularly in genetically susceptible individuals.
A method of predicting the in vitro fibril formation propensity of Aβ40 mutants based on their inclusion body levels in E. coli
Authors: Sanagavarapu Kalyani , Nüske Elisabeth , Nasir Irem , Meisl Georg , Immink Jasper N. , Sormanni Pietro , Vendruscolo Michele , Knowles Tuomas P. J. , Malmendal Anders , Cabaleiro-Lago Celia , Linse Sara 
Published: March 2019

AbstractOverexpression of recombinant proteins in bacteria may lead to their aggregation and deposition in inclusion bodies. Since the conformational properties of proteins in inclusion bodies exhibit many of the characteristics typical of amyloid fibrils. Based on these findings, we hypothesize that the rate at which proteins form amyloid fibrils may be predicted from their propensity to form inclusion bodies. To establish a method based on this concept, we first measured by SDS-PAGE and confocal microscopy the level of inclusion bodies in E. coli cells overexpressing the 40-residue amyloid-beta peptide, Aβ40, wild-type and 24 charge mutants. We then compared these results with a number of existing computational aggregation propensity predictors as well as the rates of aggregation measured in vitro for selected mutants. Our results show a strong correlation between the level of inclusion body formation and aggregation propensity, thus demonstrating the power of this approach and its value in identifying factors modulating aggregation kinetics.