bluuebunny/crossref_metadata_2025_split huggingface dataset:
Linear and inverted U-shaped dose-response functions describe estrogen effects on hippocampal activity in young women
Authors: Bayer Janine , Gläscher Jan , Finsterbusch Jürgen , Schulte Laura H. , Sommer Tobias 
Published: April 2018

AbstractIn animals, 17-beta-estradiol (E2) enhances hippocampal plasticity in a dose-dependent, monotonically increasing manner, but this relationship can also exhibit an inverted U-shaped function. To investigate E2’s dose-response function in the human hippocampus, we pharmacologically increased E2 levels in 125 naturally cycling women (who were in their low-hormone menstruation phase) to physiological (equivalent to menstrual cycle peak) and supraphysiological (equivalent to levels during early pregnancy) concentrations in a placebo-controlled design. Twenty-four hours after first E2 intake, we measured brain activity during encoding of neutral and negative pictures and then tested recognition memory 24 h after encoding. Here we report that E2 exhibits both a monotonically increasing relationship with hippocampal activity as well as an inverted U-shaped relationship, depending on the hippocampal region. Hippocampal activity exhibiting a U-shaped relationship inflects at supraphysiological E2 levels, suggesting that while E2 within physiological ranges stimulates hippocampal activity, supraphysiological ranges show opposite effects.
Quantitative 3D determination of self-assembled structures on nanoparticles using small angle neutron scattering
Authors: Luo Zhi , Marson Domenico , Ong Quy K. , Loiudice Anna , Kohlbrecher Joachim , Radulescu Aurel , Krause-Heuer Anwen , Darwish Tamim , Balog Sandor , Buonsanti Raffaella , Svergun Dmitri I. , Posocco Paola , Stellacci Francesco 
Published: April 2018

AbstractThe ligand shell (LS) determines a number of nanoparticles’ properties. Nanoparticles’ cores can be accurately characterized; yet the structure of the LS, when composed of mixture of molecules, can be described only qualitatively (e.g., patchy, Janus, and random). Here we show that quantitative description of the LS’ morphology of monodisperse nanoparticles can be obtained using small-angle neutron scattering (SANS), measured at multiple contrasts, achieved by either ligand or solvent deuteration. Three-dimensional models of the nanoparticles’ core and LS are generated using an ab initio reconstruction method. Characteristic length scales extracted from the models are compared with simulations. We also characterize the evolution of the LS upon thermal annealing, and investigate the LS morphology of mixed-ligand copper and silver nanoparticles as well as gold nanoparticles coated with ternary mixtures. Our results suggest that SANS combined with multiphase modeling is a versatile approach for the characterization of nanoparticles’ LS.
Designer exosomes produced by implanted cells intracerebrally deliver therapeutic cargo for Parkinson’s disease treatment
Authors: Kojima Ryosuke , Bojar Daniel , Rizzi Giorgio , Hamri Ghislaine Charpin-El , El-Baba Marie Daoud , Saxena Pratik , Ausländer Simon , Tan Kelly R. , Fussenegger Martin 
Published: April 2018

AbstractExosomes are cell-derived nanovesicles (50–150 nm), which mediate intercellular communication, and are candidate therapeutic agents. However, inefficiency of exosomal message transfer, such as mRNA, and lack of methods to create designer exosomes have hampered their development into therapeutic interventions. Here, we report a set of EXOsomal transfer into cells (EXOtic) devices that enable efficient, customizable production of designer exosomes in engineered mammalian cells. These genetically encoded devices in exosome producer cells enhance exosome production, specific mRNA packaging, and delivery of the mRNA into the cytosol of target cells, enabling efficient cell-to-cell communication without the need to concentrate exosomes. Further, engineered producer cells implanted in living mice could consistently deliver cargo mRNA to the brain. Therapeutic catalase mRNA delivery by designer exosomes attenuated neurotoxicity and neuroinflammation in in vitro and in vivo models of Parkinson’s disease, indicating the potential usefulness of the EXOtic devices for RNA delivery-based therapeutic applications.
Giant optical nonlinearities from Rydberg excitons in semiconductor microcavities
Authors: Walther Valentin , Johne Robert , Pohl Thomas 
Published: April 2018

AbstractThe realization of exciton polaritons—hybrid excitations of semiconductor quantum well excitons and cavity photons—has been of great technological and scientific significance. In particular, the short-range collisional interaction between excitons has enabled explorations into a wealth of nonequilibrium and hydrodynamical effects that arise in weakly nonlinear polariton condensates. Yet, the ability to enhance optical nonlinearities would enable quantum photonics applications and open up a new realm of photonic many-body physics in a scalable and engineerable solid-state environment. Here we outline a route to such capabilities in cavity-coupled semiconductors by exploiting the giant interactions between excitons in Rydberg states. We demonstrate that optical nonlinearities in such systems can be vastly enhanced by several orders of magnitude and induce nonlinear processes at the level of single photons.
Massive mining of publicly available RNA-seq data from human and mouse
Authors: Lachmann Alexander , Torre Denis , Keenan Alexandra B. , Jagodnik Kathleen M. , Lee Hoyjin J. , Wang Lily , Silverstein Moshe C. , Ma’ayan Avi 
Published: April 2018

AbstractRNA sequencing (RNA-seq) is the leading technology for genome-wide transcript quantification. However, publicly available RNA-seq data is currently provided mostly in raw form, a significant barrier for global and integrative retrospective analyses. ARCHS4 is a web resource that makes the majority of published RNA-seq data from human and mouse available at the gene and transcript levels. For developing ARCHS4, available FASTQ files from RNA-seq experiments from the Gene Expression Omnibus (GEO) were aligned using a cloud-based infrastructure. In total 187,946 samples are accessible through ARCHS4 with 103,083 mouse and 84,863 human. Additionally, the ARCHS4 web interface provides intuitive exploration of the processed data through querying tools, interactive visualization, and gene pages that provide average expression across cell lines and tissues, top co-expressed genes for each gene, and predicted biological functions and protein–protein interactions for each gene based on prior knowledge combined with co-expression.
The beta secretase BACE1 regulates the expression of insulin receptor in the liver
Authors: Meakin Paul J. , Mezzapesa Anna , Benabou Eva , Haas Mary E. , Bonardo Bernadette , Grino Michel , Brunel Jean-Michel , Desbois-Mouthon Christèle , Biddinger Sudha B. , Govers Roland , Ashford Michael L. J. , Peiretti Franck 
Published: April 2018

AbstractInsulin receptor (IR) plays a key role in the control of glucose homeostasis; however, the regulation of its cellular expression remains poorly understood. Here we show that the amount of biologically active IR is regulated by the cleavage of its ectodomain, by the β-site amyloid precursor protein cleaving enzyme 1 (BACE1), in a glucose concentration-dependent manner. In vivo studies demonstrate that BACE1 regulates the amount of IR and insulin signaling in the liver. During diabetes, BACE1-dependent cleavage of IR is increased and the amount of IR in the liver is reduced, whereas infusion of a BACE1 inhibitor partially restores liver IR. We suggest the potential use of BACE1 inhibitors to enhance insulin signaling during diabetes. Additionally, we show that plasma levels of cleaved IR reflect IR isoform A expression levels in liver tumors, which prompts us to propose that the measurement of circulating cleaved IR may assist hepatic cancer detection and management.
A NIGT1-centred transcriptional cascade regulates nitrate signalling and incorporates phosphorus starvation signals in Arabidopsis
Authors: Maeda Yoshie , Konishi Mineko , Kiba Takatoshi , Sakuraba Yasuhito , Sawaki Naoya , Kurai Tomohiro , Ueda Yoshiaki , Sakakibara Hitoshi , Yanagisawa Shuichi 
Published: April 2018

AbstractNitrate is a nutrient signal that triggers complex regulation of transcriptional networks to modulate nutrient-dependent growth and development in plants. This includes time- and nitrate concentration-dependent regulation of nitrate-related gene expression. However, the underlying mechanisms remain poorly understood. Here we identify NIGT1 transcriptional repressors as negative regulators of the ArabidopsisNRT2.1 nitrate transporter gene, and show antagonistic regulation by NLP primary transcription factors for nitrate signalling and the NLP-NIGT1 transcriptional cascade-mediated repression. This antagonistic regulation provides a resolution to the complexity of nitrate-induced transcriptional regulations. Genome-wide analysis reveals that this mechanism is applicable to NRT2.1 and other genes involved in nitrate assimilation, hormone biosynthesis and transcription. Furthermore, the PHR1 master regulator of the phosphorus-starvation response also directly promotes expression of NIGT1 family genes, leading to reductions in nitrate uptake. NIGT1 repressors thus act in two transcriptional cascades, forming a direct link between phosphorus and nitrogen nutritional regulation.
Entropy favors heterogeneous structures of networks near the rigidity threshold
Authors: Yan Le 
Published: April 2018

AbstractThe dynamical properties and mechanical functions of amorphous materials are governed by their microscopic structures, particularly the elasticity of the interaction networks, which is generally complicated by structural heterogeneity. This ubiquitous heterogeneous nature of amorphous materials is intriguingly attributed to a complex role of entropy. Here, we show in disordered networks that the vibrational entropy increases by creating phase-separated structures when the interaction connectivity is close to the onset of network rigidity. The stress energy, which conversely penalizes the heterogeneity, finally dominates a smaller vicinity of the rigidity threshold at the glass transition and creates a homogeneous intermediate phase. This picture of structures changing between homogeneous and heterogeneous phases by varying connectivity provides an interpretation of the transitions observed in chalcogenide glasses.
Statistical variances of diffusional properties from ab initio molecular dynamics simulations
Authors: He Xingfeng , Zhu Yizhou , Epstein Alexander , Mo Yifei 
Published: April 2018

AbstractAb initio molecular dynamics (AIMD) simulation is widely employed in studying diffusion mechanisms and in quantifying diffusional properties of materials. However, AIMD simulations are often limited to a few hundred atoms and a short, sub-nanosecond physical timescale, which leads to models that include only a limited number of diffusion events. As a result, the diffusional properties obtained from AIMD simulations are often plagued by poor statistics. In this paper, we re-examine the process to estimate diffusivity and ionic conductivity from the AIMD simulations and establish the procedure to minimize the fitting errors. In addition, we propose methods for quantifying the statistical variance of the diffusivity and ionic conductivity from the number of diffusion events observed during the AIMD simulation. Since an adequate number of diffusion events must be sampled, AIMD simulations should be sufficiently long and can only be performed on materials with reasonably fast diffusion. We chart the ranges of materials and physical conditions that can be accessible by AIMD simulations in studying diffusional properties. Our work provides the foundation for quantifying the statistical confidence levels of diffusion results from AIMD simulations and for correctly employing this powerful technique.
Ultra-low thermal conductivity of two-dimensional phononic crystals in the incoherent regime
Authors: Xie Guofeng , Ju Zhifang , Zhou Kuikui , Wei Xiaolin , Guo Zhixin , Cai Yongqing , Zhang Gang 
Published: April 2018

AbstractTwo-dimensional silicon phononic crystals have attracted extensive research interest for thermoelectric applications due to their reproducible low thermal conductivity and sufficiently good electrical properties. For thermoelectric devices in high-temperature environment, the coherent phonon interference is strongly suppressed; therefore phonon transport in the incoherent regime is critically important for manipulating their thermal conductivity. On the basis of perturbation theory, we present herein a novel phonon scattering process from the perspective of bond order imperfections in the surface skin of nanostructures. We incorporate this strongly frequency-dependent scattering rate into the phonon Boltzmann transport equation and reproduce the ultra low thermal conductivity of holey silicon nanostructures. We reveal that the remarkable reduction of thermal conductivity originates not only from the impediment of low-frequency phonons by normal boundary scattering, but also from the severe suppression of high-frequency phonons by surface bond order imperfections scattering. Our theory not only reveals the role of the holey surface on the phonon transport, but also provide a computation tool for thermal conductivity modification in nanostructures through surface engineering.
Electrophysiological experiments in microgravity: lessons learned and future challenges
Authors: Wuest Simon L. , Gantenbein Benjamin , Ille Fabian , Egli Marcel 
Published: April 2018

AbstractAdvances in electrophysiological experiments have led to the discovery of mechanosensitive ion channels (MSCs) and the identification of the physiological function of specific MSCs. They are believed to play important roles in mechanosensitive pathways by allowing for cells to sense their mechanical environment. However, the physiological function of many MSCs has not been conclusively identified. Therefore, experiments have been developed that expose cells to various mechanical loads, such as shear flow, membrane indentation, osmotic challenges and hydrostatic pressure. In line with these experiments, mechanical unloading, as experienced in microgravity, represents an interesting alternative condition, since exposure to microgravity leads to a series of physiological adaption processes. As outlined in this review, electrophysiological experiments performed in microgravity have shown an influence of gravity on biological functions depending on ion channels at all hierarchical levels, from the cellular level to organs. In this context, calcium signaling represents an interesting cellular pathway, as it involves the direct action of calcium-permeable ion channels, and specific gravitatic cells have linked graviperception to this pathway. Multiple key proteins in the graviperception pathways have been identified. However, measurements on vertebrae cells have revealed controversial results. In conclusion, electrophysiological experiments in microgravity have shown that ion-channel-dependent physiological processes are altered in mechanically unloaded conditions. Future experiments may provide a better understanding of the underlying mechanisms.
Milestones of low-D quantum magnetism
Authors: Vasiliev Alexander , Volkova Olga , Zvereva Elena , Markina Maria 
Published: April 2018

AbstractThere is a long time gap between the formulation of the basic theory of low-dimensional (low-D) magnetism as advanced by Ising, Heisenberg and Bethe and its experimental verification. The latter started not long before the discovery of high-TC superconductivity in cuprates and has been boosted by this discovery result in an impressive succession of newly observed physical phenomena. Milestones on this road were the compounds which reached their quantum ground states upon lowering the temperature either gradually or through different instabilities. The gapless and gapped ground states for spin excitations in these compounds are inherent for isolated half-integer spin and integer spin chains, respectively. The same is true for the compounds hosting odd and even leg spin ladders. Some complex oxides of transition metals reach gapped ground state by means of spin-Peierls transition, charge ordering or orbital ordering mechanisms. However, the overwhelming majority of low-dimensional systems arrive to a long-range ordered magnetic state, albeit quite exotic realizations. Under a magnetic field some frustrated magnets stabilize multipolar order, e.g., showing a spin-nematic state in the simplest quadropolar case. Finally, numerous square, triangular, kagome and honeycomb layered lattices, along with Shastry–Sutherland and Nersesyan–Tsvelik patterns constitute the playground to check the basic concepts of two-dimensional magnetism, including resonating valence bond state, Berezinskii–Kosterlitz–Thouless transition and Kitaev model.
A Novel Platform for Evaluating the Environmental Impacts on Bacterial Cellulose Production
Authors: Basu Anindya , Vadanan Sundaravadanam Vishnu , Lim Sierin 
Published: April 2018

AbstractBacterial cellulose (BC) is a biocompatible material with versatile applications. However, its large-scale production is challenged by the limited biological knowledge of the bacteria. The advent of synthetic biology has lead the way to the development of BC producing microbes as a novel chassis. Hence, investigation on optimal growth conditions for BC production and understanding of the fundamental biological processes are imperative. In this study, we report a novel analytical platform that can be used for studying the biology and optimizing growth conditions of cellulose producing bacteria. The platform is based on surface growth pattern of the organism and allows us to confirm that cellulose fibrils produced by the bacteria play a pivotal role towards their chemotaxis. The platform efficiently determines the impacts of different growth conditions on cellulose production and is translatable to static culture conditions. The analytical platform provides a means for fundamental biological studies of bacteria chemotaxis as well as systematic approach towards rational design and development of scalable bioprocessing strategies for industrial production of bacterial cellulose.
Cross-species analysis of apical asparagine-rich protein of Plasmodium vivax and Plasmodium knowlesi
Authors: Muh Fauzi , Ahmed Md Atique , Han Jin-Hee , Nyunt Myat Htut , Lee Seong-Kyun , Lau Yee Ling , Kaneko Osamu , Han Eun-Taek 
Published: April 2018

AbstractThe Plasmodium falciparum apical asparagine (Asn)-rich protein (AARP) is one of malarial proteins, and it has been studied as a candidate of malaria subunit vaccine. Basic characterization of PvAARP has been performed with a focus on its immunogenicity and localization. In this study, we further analyzed the immunogenicity of PvAARP, focusing on the longevity of the antibody response, cross-species immunity and invasion inhibitory activity by using the primate malaria parasite Plasmodium knowlesi. We found that vivax malaria patient sera retained anti-PvAARP antibodies for at least one year without re-infection. Recombinant PvAARP protein was strongly recognized by knowlesi malaria patients. Antibody raised against the P. vivax and P. knowlesi AARP N-termini reacted with the apical side of the P. knowlesi merozoites and inhibited erythrocyte invasion by P. knowlesi in a concentration-dependent manner, thereby suggesting a cross-species nature of anti-PvAARP antibody against PkAARP. These results can be explained by B cell epitopes predicted in conserved surface-exposed regions of the AARP N-terminus in both species. The long-lived anti-PvAARP antibody response, cross-reactivity, and invasion inhibitory activity of anti-PvAARP support a critical role of AARP during the erythrocyte invasion and suggest that PvAARP induces long-lived cross-species protective immunity against P. vivax and P. knowlesi.
Compromised functionality of monocyte-derived dendritic cells in multiple myeloma patients may limit their use in cancer immunotherapy
Authors: Shinde Prajakta , Fernandes Sophia , Melinkeri Sameer , Kale Vaijayanti , Limaye Lalita 
Published: April 2018

AbstractDendritic cells (DCs) have the potential to elicit long-lasting anti-tumour immune responses. Most of the clinical trials of anti-cancer DC vaccines are based on monocyte-derived DCs (Mo-DCs). However, their outcomes have shown limited promise especially in multiple myeloma (MM) patients. Here, we investigated whether in vitro generated Mo-DCs from MM patients (MM-DCs) possess impaired functionality, thus contributing to the limited success of DC vaccines. We generated MM-DCs and compared them with DCs from healthy donors (HD-DCs). The yield of DCs in MM was 3.5 fold lower than in HD sets. However morphology, phenotype, antigen uptake and allo-T cell stimulation were comparable. Migration and secretion of IL12p70 and IFN-γ (in DC-T cell co-cultures) were significantly reduced in MM-DCs. Thus, MM-DCs were compromised in functionality. This impairment could be attributed to autocrine secretion of IL6 by MM-monocytes and activation of their P38 MAPK pathway. This indicates a need to look for alternative sources of DCs.
A clinically relevant and bias-controlled murine model to study acute traumatic coagulopathy
Authors: Gangloff C. , Grimault O. , Theron M. , Pichavant K. , Galinat H. , Mingant F. , Ozier Y. 
Published: April 2018

AbstractAcute traumatic coagulopathy (ATC) is an acute and endogenous mechanism triggered by the association of trauma and hemorrhage. Several animal models have been developed, but some major biases have not yet been identified. Our aim was to develop a robust and clinically relevant murine model to study this condition. Anesthetized adult Sprague Dawley rats were randomized into 4 groups: C, control; T, trauma; H, hemorrhage; TH, trauma and hemorrhage (n = 7 each). Trauma consisted of laparotomy associated with four-limb and splenic fractures. Clinical variables, ionograms, arterial and hemostasis blood tests were compared at 0 and 90 min. ATC and un-compensated shock were observed in group TH. In this group, the rise in prothrombin time and activated partial thromboplastin was 29 and 40%, respectively. Shock markers, compensation mechanisms and coagulation pathways were all consistent with human pathophysiology. The absence of confounding factors, such as trauma-related bleeding or dilution due to trans-capillary refill was verified. This ethic, cost effective and bias-controlled model reproduced the specific and endogenous mechanism of ATC and will allow to identify potential targets for therapeutics in case of trauma-related hemorrhage.