bluuebunny/crossref_metadata_2025_split huggingface dataset:
Complex formation of APP with GABAB receptors links axonal trafficking to amyloidogenic processing
Authors: Dinamarca Margarita C. , Raveh Adi , Schneider Andy , Fritzius Thorsten , Früh Simon , Rem Pascal D. , Stawarski Michal , Lalanne Txomin , Turecek Rostislav , Choo Myeongjeong , Besseyrias Valérie , Bildl Wolfgang , Bentrop Detlef , Staufenbiel Matthias , Gassmann Martin , Fakler Bernd , Schwenk Jochen , Bettler Bernhard 
Published: March 2019

AbstractGABAB receptors (GBRs) are key regulators of synaptic release but little is known about trafficking mechanisms that control their presynaptic abundance. We now show that sequence-related epitopes in APP, AJAP-1 and PIANP bind with nanomolar affinities to the N-terminal sushi-domain of presynaptic GBRs. Of the three interacting proteins, selectively the genetic loss of APP impaired GBR-mediated presynaptic inhibition and axonal GBR expression. Proteomic and functional analyses revealed that APP associates with JIP and calsyntenin proteins that link the APP/GBR complex in cargo vesicles to the axonal trafficking motor. Complex formation with GBRs stabilizes APP at the cell surface and reduces proteolysis of APP to Aβ, a component of senile plaques in Alzheimer’s disease patients. Thus, APP/GBR complex formation links presynaptic GBR trafficking to Aβ formation. Our findings support that dysfunctional axonal trafficking and reduced GBR expression in Alzheimer’s disease increases Aβ formation.
Hippocampal CA1 replay becomes less prominent but more rigid without inputs from medial entorhinal cortex
Authors: Chenani Alireza , Sabariego Marta , Schlesiger Magdalene I. , Leutgeb Jill K. , Leutgeb Stefan , Leibold Christian 
Published: March 2019

AbstractThe hippocampus is an essential brain area for learning and memory. However, the network mechanisms underlying memory storage, consolidation and retrieval remain incompletely understood. Place cell sequences during theta oscillations are thought to be replayed during non-theta states to support consolidation and route planning. In animals with medial entorhinal cortex (MEC) lesions, the temporal organization of theta-related hippocampal activity is disrupted, which allows us to test whether replay is also compromised. Two different analyses—comparison of co-activation patterns between running and rest epochs and analysis of the recurrence of place cell sequences—reveal that the enhancement of replay by behavior is reduced in MEC-lesioned versus control rats. In contrast, the degree of intrinsic network structure prior and subsequent to behavior remains unaffected by MEC lesions. The MEC-dependent temporal coordination during theta states therefore appears to facilitate behavior-related plasticity, but does not disrupt pre-existing functional connectivity.
Phototrophic extracellular electron uptake is linked to carbon dioxide fixation in the bacterium Rhodopseudomonas palustris
Authors: Guzman Michael S. , Rengasamy Karthikeyan , Binkley Michael M. , Jones Clive , Ranaivoarisoa Tahina Onina , Singh Rajesh , Fike David A. , Meacham J. Mark , Bose Arpita 
Published: March 2019

AbstractExtracellular electron uptake (EEU) is the ability of microbes to take up electrons from solid-phase conductive substances such as metal oxides. EEU is performed by prevalent phototrophic bacterial genera, but the electron transfer pathways and the physiological electron sinks are poorly understood. Here we show that electrons enter the photosynthetic electron transport chain during EEU in the phototrophic bacterium Rhodopseudomonas palustris TIE-1. Cathodic electron flow is also correlated with a highly reducing intracellular redox environment. We show that reducing equivalents are used for carbon dioxide (CO2) fixation, which is the primary electron sink. Deletion of the genes encoding ruBisCO (the CO2-fixing enzyme of the Calvin-Benson-Bassham cycle) leads to a 90% reduction in EEU. This work shows that phototrophs can directly use solid-phase conductive substances for electron transfer, energy transduction, and CO2 fixation.
Numerical representations for flow velocity and shear rate inside electromagnetically levitated droplets in microgravity
Authors: Xiao Xiao , Lee Jonghyun , Hyers Robert W. , Matson Douglas M. 
Published: March 2019

AbstractElectromagnetic levitation techniques are used in a microgravity environment to allow materials research under containerless conditions while limiting the influence of gravity. The induced advective flow inside a levitated molten alloy droplet is a key factor affecting solidification phenomena while potentially influencing the measurement of thermophysical properties of metallic alloy. It is thus important to predict the flow velocity under various operation conditions during melt processing. In this work, a magnetohydrodynamic model is applied over the range of conditions under which electromagnetically levitated droplets are processed to represent the maximum flow velocity and shear rate as a polynomial function of heating voltage, density, viscosity, and electrical conductivity of molten materials. An example is given for the ternary steel alloy Fe-19Cr-21Ni (at%) to demonstrate how internal advection under different heater settings becomes a strong function of alloy temperature and is a determining factor in the transition from laminar to turbulent flow conditions. The results are directly applicable to a range of other materials with properties in the range considered, including Ni-based superalloys, Ti-6Al-4V, and many other commercially-important alloys.
A prophylactic α-Gal-based glycovaccine effectively protects against murine acute Chagas disease
Authors: Portillo Susana , Zepeda Brenda G. , Iniguez Eva , Olivas Janet J. , Karimi Nasim H. , Moreira Otacilio C. , Marques Alexandre F. , Michael Katja , Maldonado Rosa A. , Almeida Igor C. 
Published: March 2019

AbstractChagas disease (ChD), caused by the hemoflagellate parasiteTrypanosoma cruzi, affects six to seven million people in Latin America. Lately, it has become an emerging public health concern in nonendemic regions such as North America and Europe. There is no prophylactic or therapeutic vaccine as yet, and current chemotherapy is rather toxic and has limited efficacy in the chronic phase of the disease. The parasite surface is heavily coated by glycoproteins such as glycosylphosphatidylinositol (GPI)-anchored mucins (tGPI-mucins), which display highly immunogenic terminal nonreducing α-galactopyranosyl (α-Gal)-containing glycotopes that are entirely absent in humans. The immunodominant tGPI-mucin α-Gal glycotope, the trisaccharide Galα1,3Galβ1,4GlcNAc (Galα3LN), elicits high levels of protectiveT.cruzi-specific anti-α-Gal antibodies in ChD patients in both the acute and chronic phases. Although glycoconjugates are the major parasite glycocalyx antigens, they remain completely unexplored as potential ChD vaccine candidates. Here we investigate the efficacy of theT.cruziimmunodominant glycotope Galα3LN, covalently linked to a carrier protein (human serum albumin (HSA)), as a prophylactic vaccine candidate in the acute model of ChD, using the α1,3-galactosyltransferase-knockout (α1,3GalT-KO) mouse, which mimics the human immunoresponse to α-Gal glycotopes. Animals vaccinated with Galα3LN-HSA were fully protected against lethalT.cruzichallenge by inducing a strong anti-α-Gal antibody-mediated humoral response. Furthermore, Galα3LN-HSA-vaccinated α1,3GalT-KO mice exhibited significant reduction (91.7–99.9%) in parasite load in all tissues analyzed, cardiac inflammation, myocyte necrosis, and T cell infiltration. This is a proof-of-concept study to demonstrate the efficacy of a prophylactic α-Gal-based glycovaccine for experimental acute Chagas disease.
The variations in the East Asian summer monsoon over the past 3 kyrs and the controlling factors
Authors: Yamada Katsura , Kohara Kazuma , Ikehara Minoru , Seto Koji 
Published: March 2019

AbstractThe mechanisms driving the variations in the centennial-scale East Asian summer monsoon (EASM) remain unclear. Here, we use the δ18O records from adult ostracode shells to reconstruct the EASM variations over the last 3 kyrs in southwestern Japan. A common variation with a 200 yr periodicity among the Asian monsoonal regions was recognized between BC 800 and BC 100. Since then, neither a correlation between the EASM variation and solar activity or a common EASM variation through EASM regions has been identified. The evidence reveals that solar activity dominantly affected the centennial-scale EASM variations throughout Asian monsoonal regions until BC 100. Furthermore, factors other than solar activity that varied and differed in specific regions controlled the EASM intensity due to decreasing summer solar insolation in the Northern Hemisphere after BC 100. These relations indicate that the dominant factor that affects the EASM variations shifts according to the solar insolation intensity.
Genome-Wide Association Study of Major Agronomic Traits in Foxtail Millet (Setaria italica L.) Using ddRAD Sequencing
Authors: Jaiswal Vandana , Gupta Sarika , Gahlaut Vijay , Muthamilarasan Mehanathan , Bandyopadhyay Tirthankar , Ramchiary Nirala , Prasad Manoj 
Published: March 2019

AbstractFoxtail millet (Setaria italica), the second largest cultivated millet crop after pearl millet, is utilized for food and forage globally. Further, it is also considered as a model crop for studying agronomic, nutritional and biofuel traits. In the present study, a genome-wide association study (GWAS) was performed for ten important agronomic traits in 142 foxtail millet core eco-geographically diverse genotypes using 10 K SNPs developed through GBS-ddRAD approach. Number of SNPs on individual chromosome ranged from 844 (chromosome 5) to 2153 (chromosome 8) with an average SNP frequency of 25.9 per Mb. The pairwise linkage disequilibrium (LD) estimated using the squared-allele frequency correlations was found to decay rapidly with the genetic distance of 177 Kb. However, for individual chromosome, LD decay distance ranged from 76 Kb (chromosome 6) to 357 Kb (chromosome 4). GWAS identified 81 MTAs (marker-trait associations) for ten traits across the genome. High confidence MTAs for three important agronomic traits including FLW (flag leaf width), GY (grain yield) and TGW (thousand-grain weight) were identified. Significant pyramiding effect of identified MTAs further supplemented its importance in breeding programs. Desirable alleles and superior genotypes identified in the present study may prove valuable for foxtail millet improvement through marker-assisted selection.
Mechanism for the Structural Transformation to the Modulated Superconducting Phase of Compressed Hydrogen Sulfide
Authors: Majumdar Arnab , Tse John S. , Yao Yansun 
Published: March 2019

AbstractA comprehensive description of crystal and electronic structures, structural transformations, and pressure-dependent superconducting temperature (Tc) of hydrogen sulfide (H2S) compressed from low pressure is presented through the analysis of the results from metadynamics simulations. It is shown that local minimum metastable crystal structures obtained are dependent on the choice of pressure-temperature thermodynamic paths. The origin of the recently proposed ‘high-Tc’ superconducting phase with a modulated structure and a diffraction pattern reproducing two independent experiments was the low pressure Pmc21 structure. This Pmc21 structure is found to transform to a Pc structure at 80 K and 80 GPa which becomes metallic and superconductive above 100 GPa. This structure becomes dynamically unstable above 140 GPa beyond which phonon instability sets in at about a quarter in the Γ to Y segment. This explains the transformation to a 1:3 modulation structure at high pressures proposed previously. The pressure trend of the calculated Tc for the Pc structure is consistent with the experimentally measured ‘low-Tc phase’. Fermi surface analysis hints that pressurized hydrogen sulfide may be a multi-band superconductor. The theoretical results reproduced many experimental characteristics, suggesting that the dissociation of H2S is unrequired to explain the superconductivity of compressed H2S at any pressure.
Frontal and parietal alpha oscillations reflect attentional modulation of cross-modal matching
Authors: Misselhorn Jonas , Friese Uwe , Engel Andreas K. 
Published: March 2019

AbstractMultisensory perception is shaped by both attentional selection of relevant sensory inputs and exploitation of stimulus-driven factors that promote cross-modal binding. Underlying mechanisms of both top-down and bottom-up modulations have been linked to changes in alpha/gamma dynamics in primary sensory cortices and temporoparietal cortex. Accordingly, it has been proposed that alpha oscillations provide pulsed inhibition for gamma activity and thereby dynamically route cortical information flow. In this study, we employed a recently introduced multisensory paradigm incorporating both bottom-up and top-down aspects of cross-modal attention in an EEG study. The same trimodal stimuli were presented in two distinct attentional conditions, focused on visual-tactile or audio-visual components, for which cross-modal congruence of amplitude changes had to be evaluated. Neither top-down nor bottom-up cross-modal attention modulated alpha or gamma power in primary sensory cortices. Instead, we found alpha band effects in bilateral frontal and right parietal cortex. We propose that frontal alpha oscillations reflect the origin of top-down control regulating perceptual gains and that modulations of parietal alpha oscillations relates to intersensory re-orienting. Taken together, we suggest that the idea of selective cortical routing via alpha oscillations can be extended from sensory cortices to the frontoparietal attention network.
Evaluating digital medicine ingestion data from seriously mentally ill patients with a Bayesian Hybrid Model
Authors: Knights Jonathan , Heidary Zahra , Peters-Strickland Timothy , Ramanathan Murali 
Published: March 2019

AbstractThe objective of this work was to adapt and evaluate the performance of a Bayesian hybrid model to characterize objective temporal medication ingestion parameters from two clinical studies in patients with serious mental illness (SMI) receiving treatment with a digital medicine system. This system provides a signal from an ingested sensor contained in the dosage form to a patient-worn patch and transmits this signal via the patient’s mobile device. A previously developed hybrid Markov-von Mises model was used to obtain maximum-likelihood estimates for medication ingestion behavior parameters for individual patients. The individual parameter estimates were modeled to obtain distribution parameters of priors implemented in a Markov chain-Monte Carlo framework. Clinical and demographic covariates associated with model ingestion parameters were also assessed. We obtained individual estimates of overall observed ingestion percent (median:75.9%, range:18.2–98.3%, IQR:32.9%), rate of excess dosing events (median:0%, range:0–14.3%, IQR:3.0%) and observed ingestion duration. The modeling also provided estimates of the Markov-dependence probabilities of dosing success following a dosing success or failure. The ingestion-timing deviations were modeled with the von Mises distribution. A subset of 17 patients (22.1%) were identified as prompt correctors based on Markov-dependence probability of a dosing failure followed by a dosing success of unity. The prompt corrector sub-group had a better overall digital medicine ingestion parameter profile compared to those who were not prompt correctors. Our results demonstrate the potential utility of a Bayesian Hybrid Markov-von Mises model for characterizing digital medicine ingestion patterns in patients with SMI.
Disease-associated mutations of claudin-19 disrupt retinal neurogenesis and visual function
Authors: Wang Shao-Bin , Xu Tao , Peng Shaomin , Singh Deepti , Ghiassi-Nejad Maryam , Adelman Ron A. , Rizzolo Lawrence J. 
Published: March 2019

AbstractMutations of claudin-19 cause Familial Hypomagnesaemia and Hypercalciuria, Nephrocalcinosis with Ocular Involvement. To study the ocular disease without the complications of the kidney disease, naturally occurring point mutations of human CLDN19 were recreated in human induced pluripotent cells or overexpressed in the retinae of newborn mice. In human induced pluripotent cells, we show that the mutation affects retinal neurogenesis and maturation of retinal pigment epithelium (RPE). In mice, the mutations diminish the P1 wave of the electroretinogram, activate apoptosis in the outer nuclear layer, and alter the morphology of bipolar cells. If mice are given 9-cis-retinal to counter the loss of retinal isomerase, the P1 wave is partially restored. The ARPE19 cell line fails to express claudin-19. Exogenous expression of wild type, but not mutant claudin-19, increases the expression of RPE signature genes. Mutated claudin-19 affects multiple stages of RPE and retinal differentiation through its effects on multiple functions of the RPE.
cIAP1 promotes proliferation and migration and prevents apoptosis in gallbladder cancer in vitro
Authors: Su Wei , Jiang Xiaojie , Chen Mingyuan , Huang Maotuan , Tang Nanhong , Wang Xiaoqian , Li Xiujin , She Feifei , Chen Yanlin 
Published: March 2019

Abstract
Gallbladder cancer (GBC) is a demanding fatal disease with no ideal treatment for inoperable patients. Recent reports have determined TNF-α associated lymphatic metastasis in GBC, while its resistance to TNF-α-killing remains largely unexplored. In this assay, we first found cellular inhibitor of apoptosis (cIAP1) overexpressed in GBC tissues and the roles in promoting the proliferation and migration of GBC in vitro as its homology cIAP2 does. Then how GBC cell survives TNF-α toxicity and TNF-α-induced apoptosis first prevail as follows. The reduction in cIAP1 does not give rise to apoptosis even with the stimulation of TNF-α. Importantly, the loss of cIAP1 enhanced TNF-α/cycloheximide-induced apoptosis in higher activation statuses of Caspase-8, Caspase-3 without the induction of Complex Ⅱ. In response to TNF-α, the reduction in cIAP1 caused the suppression in nuclear factor-κB (NF-κB) pathway and inhibition of transcription of cell death regulator cellular FLICE-like Inhibitory Protein (c-FLIP) instead. To conclude, cIAP1 is an oncological protein abundant in GBC tissues, which enhances proliferation and immigration and blocks TNF-α from apoptosis through NF-κB pathway in vitro.
The histone chaperoning pathway: from ribosome to nucleosome
Authors: Pardal Alonso J. , Fernandes-Duarte Filipe , Bowman Andrew J. 
Published: March 2019

Abstract
Nucleosomes represent the fundamental repeating unit of eukaryotic DNA, and comprise eight core histones around which DNA is wrapped in nearly two superhelical turns. Histones do not have the intrinsic ability to form nucleosomes; rather, they require an extensive repertoire of interacting proteins collectively known as ‘histone chaperones’. At a fundamental level, it is believed that histone chaperones guide the assembly of nucleosomes through preventing non-productive charge-based aggregates between the basic histones and acidic cellular components. At a broader level, histone chaperones influence almost all aspects of chromatin biology, regulating histone supply and demand, governing histone variant deposition, maintaining functional chromatin domains and being co-factors for histone post-translational modifications, to name a few. In this essay we review recent structural insights into histone-chaperone interactions, explore evidence for the existence of a histone chaperoning ‘pathway’ and reconcile how such histone-chaperone interactions may function thermodynamically to assemble nucleosomes and maintain chromatin homeostasis.
Post-translational modifications and chromatin dynamics
Authors: Tolsma Thomas O. , Hansen Jeffrey C. 
Published: March 2019

Abstract
The dynamic structure of chromatin is linked to gene regulation and many other biological functions. Consequently, it is of importance to understand the factors that regulate chromatin dynamics. While the in vivo analysis of chromatin has verified that histone post-translational modifications play a role in modulating DNA accessibility, the complex nuclear environment and multiplicity of modifications prevents clear conclusions as to how individual modifications influence chromatin dynamics in the cell. For this reason, in vitro analyses of model reconstituted nucleosomal arrays has been pivotal in understanding the dynamic nature of chromatin compaction and the affects that specific post-translational modifications can have on the higher order chromatin structure. In this mini-review, we briefly describe the dynamic chromatin structures that have been observed in vitro and the environmental conditions that give rise to these various conformational states. Our focus then turns to a discussion of the specific histone post-translational modifications that have been shown to alter formation of these higher order chromatin structures in vitro and how this may relate to the biological state and accessibility of chromatin in vivo.
Analysis of full disc Ca II K spectroheliograms
Authors: Chatzistergos Theodosios , Ermolli Ilaria , Krivova Natalie A. , Solanki Sami K. 
Published: March 2019

Context. Reconstructions of past irradiance variations require suitable data on solar activity. The longest direct proxy is the sunspot number, and it has been most widely employed for this purpose. These data, however, only provide information on the surface magnetic field emerging in sunspots, while a suitable proxy of the evolution of the bright magnetic features, specifically faculae/plage and network, is missing. This information can potentially be extracted from the historical full-disc observations in the Ca II K line.
Aims. We use several historical archives of full-disc Ca II K observations to derive plage areas over more than a century. Employment of different datasets allows the identification of systematic effects in the images, such as changes in instruments and procedures, as well as an assessment of the uncertainties in the results.
Methods. We have analysed over 100 000 historical images from eight digitised photographic archives of the Arcetri, Kodaikanal, McMath-Hulbert, Meudon, Mitaka, Mt Wilson, Schauinsland, and Wendelstein observatories, and one archive of modern observations from the Rome/PSPT. The analysed data cover the period 1893–2018. We first performed careful photometric calibration and compensation for the centre-to-limb variation, and then segmented the images to identify plage regions. This has been consistently applied to both historical and modern observations.
Results. The plage series derived from different archives are generally in good agreement with each other. However, there are also clear deviations that most likely hint at intrinsic differences in the data and their digitisation. We showed that accurate image processing significantly reduces errors in the plage area estimates. Accurate photometric calibration also allows precise plage identification on images from different archives without the need to arbitrarily adjust the segmentation parameters. Finally, by comparing the plage area series from the various records, we found the conversion laws between them. This allowed us to produce a preliminary composite of the plage areas obtained from all the datasets studied here. This is a first step towards an accurate assessment of the long-term variation of plage regions.