bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Gate Hinge Controls the Epithelial Calcium Channel TRPV5
Authors: van der Wijst Jenny , Leunissen Elizabeth H. , Blanchard Maxime G. , Venselaar Hanka , Verkaart Sjoerd , Paulsen Candice E. , Bindels René J. , Hoenderop Joost G. 
Published: April 2017

AbstractTRPV5 is unique within the large TRP channel family for displaying a high Ca2+ selectivity together with Ca2+-dependent inactivation. Our study aims to uncover novel insights into channel gating through in-depth structure-function analysis. We identify an exceptional tryptophan (W583) at the terminus of the intracellular pore that is unique for TRPV5 (and TRPV6). A combination of site-directed mutagenesis, biochemical and electrophysiological analysis, together with homology modeling, demonstrates that W583 is part of the gate for Ca2+ permeation. The W583 mutants show increased cell death due to profoundly enhanced Ca2+ influx, resulting from altered channel function. A glycine residue above W583 might act as flexible linker to rearrange the tryptophan gate. Furthermore, we hypothesize functional crosstalk between the pore region and carboxy terminus, involved in Ca2+-calmodulin-mediated inactivation. This study proposes a unique channel gating mechanism and delivers detailed molecular insight into the Ca2+ permeation pathway that can be extrapolated to other Ca2+-selective channels.
Giant Magnetoresistive Biosensors for Time-Domain Magnetorelaxometry: A Theoretical Investigation and Progress Toward an Immunoassay
Authors: Huang Chih-Cheng , Zhou Xiahan , Hall Drew A. 
Published: April 2017

AbstractMagnetorelaxometry (MRX) is a promising new biosensing technique for point-of-care diagnostics. Historically, magnetic sensors have been primarily used to monitor the stray field of magnetic nanoparticles bound to analytes of interest for immunoassays and flow cytometers. In MRX, the magnetic nanoparticles (MNPs) are first magnetized and then the temporal response is monitored after removing the magnetic field. This new sensing modality is insensitive to the magnetic field homogeneity making it more amenable to low-power portable applications. In this work, we systematically investigated time-domain MRX by measuring the signal dependence on the applied field, magnetization time, and magnetic core size. The extracted characteristic times varied for different magnetic MNPs, exhibiting unique magnetic signatures. We also measured the signal contribution based on the MNP location and correlated the coverage with measured signal amplitude. Lastly, we demonstrated, for the first time, a GMR-based time-domain MRX bioassay. This approach validates the feasibility of immunoassays using GMR-based MRX and provides an alternative platform for point-of-care diagnostics.
Cortical laminar tau deposits and activated astrocytes in Alzheimer’s disease visualised by 3H-THK5117 and 3H-deprenyl autoradiography
Authors: Lemoine Laetitia , Saint-Aubert Laure , Nennesmo Inger , Gillberg Per-Göran , Nordberg Agneta 
Published: April 2017

AbstractHyperphosphorylated tau protein deposits and, inflammatory processes are characteristic components of Alzheimer disease (AD) pathology. We here aimed to visualize in vitro the distribution of tau deposits and activated astrocytes across the cortical layers in autopsy AD brain tissue using the radiotracers 3H-THK5117 and 3H-deprenyl. 3H-THK5117 and 3H-deprenyl autoradiographies were carried out on frozen brain sections from three AD patients and one healthy control. 3H-THK5117 showed a distinct laminar cortical binding similar to 3H-deprenyl autoradiography, with an extensive binding in the superficial and deep layers of the temporal neocortices, whereas the middle frontal gyrus showed an even binding throughout the layers. Globally, eventhough some differences could be observed, AT8 (tau) and GFAP (astrocyte) immunostaining showed a laminar pattern comparable to their corresponding radiotracers within each AD case. Some variability was observed between the AD cases reflecting differences in disease phenotype. The similar laminar cortical brain distribution of tau deposits and activated astrocytes supports the hypothesis of a close pathological interconnection. The difference in regional binding patterns of 3H-THK5117 and AT8 antibody staining suggest additional tau binding sites detectable by 3H-THK5117.
Protein S Heerlen mutation heterozygosity is associated with venous thrombosis risk
Authors: Suchon P. , Germain M. , Delluc A. , Smadja D. , Jouven X. , Gyorgy B. , Saut N. , Ibrahim M. , Deleuze J. F. , Alessi M. C. , Morange P. E. , Trégouët D. A. 
Published: April 2017

AbstractHereditary Protein S (PS) deficiency is a rare coagulation disorder associated with an increased risk of venous thrombosis (VT). The PS Heerlen (PSH) mutation is a rare S501P mutation that was initially considered to be a neutral polymorphism. However, it has been later shown that PSH has a reduced half-life in vivo which may explain the association of PSH heterozygosity with mildly reduced levels of plasma free PS (FPS). Whether the risk of VT is increased in PSH carriers remains unknown. We analyzed the association of PSH (rs121918472 A/G) with VT in 4,173 VT patients and 5,970 healthy individuals from four independent case-control studies. Quantitative determination of FPS levels was performed in a subsample of 1257 VT patients. In the investigated populations, the AG genotype was associated with an increased VT risk of 6.57 [4.06–10.64] (p = 1.73 10−14). In VT patients in whom PS deficiency was excluded, plasma FPS levels were significantly lower in individuals with PSH when compared to those without [72 + 13 vs 91 + 21 UI/dL; p = 1.86 10−6, mean + SD for PSH carriers (n = 21) or controls (n = 1236) respectively]. We provide strong evidence that the rare PSH variant is associated with VT in unselected individuals.
Atomic structure and electronic properties of MgO grain boundaries in tunnelling magnetoresistive devices
Authors: Bean Jonathan J. , Saito Mitsuhiro , Fukami Shunsuke , Sato Hideo , Ikeda Shoji , Ohno Hideo , Ikuhara Yuichi , McKenna Keith P. 
Published: April 2017

AbstractPolycrystalline metal oxides find diverse applications in areas such as nanoelectronics, photovoltaics and catalysis. Although grain boundary defects are ubiquitous their structure and electronic properties are very poorly understood since it is extremely challenging to probe the structure of buried interfaces directly. In this paper we combine novel plan-view high-resolution transmission electron microscopy and first principles calculations to provide atomic level understanding of the structure and properties of grain boundaries in the barrier layer of a magnetic tunnel junction. We show that the highly [001] textured MgO films contain numerous tilt grain boundaries. First principles calculations reveal how these grain boundaries are associated with locally reduced band gaps (by up to 3 eV). Using a simple model we show how shunting a proportion of the tunnelling current through grain boundaries imposes limits on the maximum magnetoresistance that can be achieved in devices.
The classical correlation limits the ability of the measurement-induced average coherence
Authors: Zhang Jun , Yang Si-ren , Zhang Yang , Yu Chang-shui 
Published: April 2017

AbstractCoherence is the most fundamental quantum feature in quantum mechanics. For a bipartite quantum state, if a measurement is performed on one party, the other party, based on the measurement outcomes, will collapse to a corresponding state with some probability and hence gain the average coherence. It is shown that the average coherence is not less than the coherence of its reduced density matrix. In particular, it is very surprising that the extra average coherence (and the maximal extra average coherence with all the possible measurements taken into account) is upper bounded by the classical correlation of the bipartite state instead of the quantum correlation. We also find the sufficient and necessary condition for the null maximal extra average coherence. Some examples demonstrate the relation and, moreover, show that quantum correlation is neither sufficient nor necessary for the nonzero extra average coherence within a given measurement. In addition, the similar conclusions are drawn for both the basis-dependent and the basis-free coherence measure.
Model-independent particle species disentanglement by X-ray cross-correlation scattering
Authors: Pedrini B. , Menzel A. , Guzenko V. A. , David C. , Abela R. , Gutt C. 
Published: April 2017

AbstractMixtures of different particle species are often investigated using the angular averages of the scattered X-ray intensity. The number of species is deduced by singular value decomposition methods. The full disentanglement of the data into per-species contributions requires additional knowledge about the system under investigation. We propose to exploit higher-order angular X-ray intensity correlations with a new computational protocol, which we apply to synchrotron data from two-species mixtures of two-dimensional static test nanoparticles. Without any other information besides the correlations, we demonstrate the assessment of particle species concentrations in the measured data sets, as well as the full ab initio reconstruction of both particle structures. The concept extends straightforwardly to more species and to the three-dimensional case, whereby the practical application will require the measurements to be performed at an X-ray free electron laser.
Isolation of Circulating Plasma Cells in Multiple Myeloma Using CD138 Antibody-Based Capture in a Microfluidic Device
Authors: Qasaimeh Mohammad A. , Wu Yichao C. , Bose Suman , Menachery Anoop , Talluri Srikanth , Gonzalez Gabriel , Fulciniti Mariateresa , Karp Jeffrey M. , Prabhala Rao H. , Karnik Rohit 
Published: April 2017

AbstractThe necessity for bone marrow aspiration and the lack of highly sensitive assays to detect residual disease present challenges for effective management of multiple myeloma (MM), a plasma cell cancer. We show that a microfluidic cell capture based on CD138 antigen, which is highly expressed on plasma cells, permits quantitation of rare circulating plasma cells (CPCs) in blood and subsequent fluorescence-based assays. The microfluidic device is based on a herringbone channel design, and exhibits an estimated cell capture efficiency of ~40–70%, permitting detection of <10 CPCs/mL using 1-mL sample volumes, which is difficult using existing techniques. In bone marrow samples, the microfluidic-based plasma cell counts exhibited excellent correlation with flow cytometry analysis. In peripheral blood samples, the device detected a baseline of 2–5 CD138+ cells/mL in healthy donor blood, with significantly higher numbers in blood samples of MM patients in remission (20–24 CD138+ cells/mL), and yet higher numbers in MM patients exhibiting disease (45–184 CD138+ cells/mL). Analysis of CPCs isolated using the device was consistent with serum immunoglobulin assays that are commonly used in MM diagnostics. These results indicate the potential of CD138-based microfluidic CPC capture as a useful ‘liquid biopsy’ that may complement or partially replace bone marrow aspiration.
Human induced-pluripotent stem cell-derived hepatocyte-like cells as an in vitro model of human hepatitis B virus infection
Authors: Sakurai Fuminori , Mitani Seiji , Yamamoto Tatsuro , Takayama Kazuo , Tachibana Masashi , Watashi Koichi , Wakita Takaji , Iijima Sayuki , Tanaka Yasuhito , Mizuguchi Hiroyuki 
Published: April 2017

AbstractIn order to understand the life cycle of hepatitis B virus (HBV) and to develop efficient anti-HBV drugs, a usefulin vitrocell culture system which allows HBV infection and recapitulates virus-host interactions is essential; however, pre-existingin vitroHBV infection models are often problematic. Here, we examined the potential of human induced-pluripotent stem (iPS) cell-derived hepatocyte-like cells (iPS-HLCs) as anin vitroHBV infection model. Expression levels of several genes involved in HBV infection, including the sodium taurocholate cotransporting polypeptide (NTCP) gene, were gradually elevated as the differentiation status of human iPS cells proceeded to iPS-HLCs. The mRNA levels of these genes were comparable between primary human hepatocytes (PHHs) and iPS-HLCs. Following inoculation with HBV, we found significant production of HBV proteins and viral RNAs in iPS-HLCs. The three major forms of the HBV genome were detected in iPS-HLCs by Southern blotting analysis. Anti-HBV agents entecavir and Myrcludex-B, which are a nucleoside analogue reverse transcriptase inhibitor and a synthetic pre-S1 peptide, respectively, significantly inhibited HBV infection in iPS-HLCs. These data demonstrate that iPS-HLCs can be used as a promisingin vitroHBV infection model.
Signatures of a macroscopic switching transition for a dynamic microtubule
Authors: Aparna J. S. , Padinhateeri Ranjith , Das Dibyendu 
Published: April 2017

AbstractCharacterising complex kinetics of non-equilibrium self-assembly of bio-filaments is of general interest. Dynamic instability in microtubules, consisting of successive catastrophes and rescues, is observed to occur as a result of the non-equilibrium conversion of GTP-tubulin to GDP-tubulin. We study this phenomenon using a model for microtubule kinetics with GTP/GDP state-dependent polymerisation, depolymerisation and hydrolysis of subunits. Our results reveal a sharp switch-like transition in the mean velocity of the filaments, from a growth phase to a shrinkage phase, with an associated co-existence of the two phases. This transition is reminiscent of the discontinuous phase transition across the liquid-gas boundary. We probe the extent of discontinuity in the transition quantitatively using characteristic signatures such as bimodality in velocity distribution, variance and Binder cumulant, and also hysteresis behaviour of the system. We further investigate ageing behaviour in catastrophes of the filament, and find that the multi-step nature of catastrophes is intensified in the vicinity of the switching transition. This assumes importance in the context of Microtubule Associated Proteins which have the potential of altering kinetic parameter values.
Identification of conserved proteins from diverse shell matrix proteome in Crassostrea gigas: characterization of genetic bases regulating shell formation
Authors: Feng Dandan , Li Qi , Yu Hong , Kong Lingfeng , Du Shaojun 
Published: April 2017

AbstractThe calcifying shell is an excellent model for studying biomineralization and evolution. However, the molecular mechanisms of shell formation are only beginning to be elucidated in Mollusca. It is known that shell matrix proteins (SMPs) play important roles in shell formation. With increasing data of shell matrix proteomes from various species, we carried out a BLASTp bioinformatics analysis using the shell matrix proteome from Crassostrea gigas against 443 SMPs from nine other species. The highly conserved tyrosinase and chitin related proteins were identified in bivalve. In addition, the relatively conserved proteins containing domains of carbonic anhydrase, Sushi, Von Willebrand factor type A, and chitin binding, were identified from all the ten species. Moreover, 25 genes encoding SMPs were annotated and characterized that are involved in CaCO3 crystallization and represent chitin related or ECM related proteins. Together, data from these analyses provide new knowledge underlying the molecular mechanism of shell formation in C.gigas, supporting a refined shell formation model including chitin and ECM-related proteins.
The impact of deep-tier burrow systems in sediment mixing and ecosystem engineering in early Cambrian carbonate settings
Authors: Zhang Li-Jun , Qi Yong-An , Buatois Luis A. , Mángano M. Gabriela , Meng Yao , Li Da 
Published: April 2017

AbstractBioturbation plays a substantial role in sediment oxygen concentration, chemical cycling, regeneration of nutrients, microbial activity, and the rate of organic matter decomposition in modern oceans. In addition, bioturbators are ecosystem engineers which promote the presence of some organisms, while precluding others. However, the impact of bioturbation in deep time remains controversial and limited sediment mixing has been indicated for early Paleozoic seas. Our understanding of the actual impact of bioturbation early in the Phanerozoic has been hampered by the lack of detailed analysis of the functional significance of specific burrow architectures. Integration of ichnologic and sedimentologic evidence from North China shows that deep-tierThalassinoidesmazes occur in lower Cambrian nearshore carbonate sediments, leading to intense disruption of the primary fabric. Comparison with modern studies suggest that some of the effects of this style of Cambrian bioturbation may have included promotion of nitrogen and ammonium fluxes across the sediment-water interface, average deepening of the redox discontinuity surface, expansion of aerobic bacteria, and increase in the rate of organic matter decomposition and the regeneration of nutrients. Our study suggests that early Cambrian sediment mixing in carbonate settings may have been more significant than assumed in previous models.
Transcription factors regulate GPR91-mediated expression of VEGF in hypoxia-induced retinopathy
Authors: Li Tingting , Hu Jianyan , Gao Fengjuan , Du Xinhua , Chen Yongdong , Wu Qiang 
Published: April 2017

AbstractHypoxia is the most important factor in the pathogenesis of diabetic retinopathy (DR). Our previous studies demonstrated that G protein-coupled receptor 91(GPR91) participated in the regulation of vascular endothelial growth factor (VEGF) secretion in DR. The present study induced OIR model in newborn rats using exposure to alternating 24-hour episodes of 50% and 12% oxygen for 14 days. Treatment with GPR91 shRNA attenuated the retinal avascular area, abnormal neovascularization and pericyte loss. Western blot and qRT-PCR demonstrated that CoCl2 exposure promoted VEGF expression and secretion, activated the ERK1/2 signaling pathways and upregulated C/EBP and AP-1. Knockdown of GPR91 inhibited ERK1/2 activity. GPR91 siRNA transduction and the ERK1/2 inhibitor U0126 inhibited the increases in C/EBP β, C/EBP δ, c-Fos and HIF-1α. Luciferase reporter assays and a chromatin immunoprecipitation (ChIP) assay demonstrated that C/EBP β and c-Fos bound the functional transcriptional factor binding site in the region of the VEGF promoter, but not C/EBP δ. Knockdown of C/EBP β and c-Fos using RNAi reduced VEGF expression. Our data suggest that activation of the GPR91-ERK1/2-C/EBP β (c-Fos, HIF-1α) signaling pathway plays a tonic role in regulating VEGF transcription in rat retinal ganglion cells.
New insight into magneto-structural phase transitions in layered TbMn2Ge2-based compounds
Authors: Fang Chunsheng , Li Guoxing , Wang Jianli , Hutchison W. D. , Ren Q. Y. , Deng Zhenyan , Ma Guohong , Dou Shixue , Campbell S. J. , Cheng Zhenxiang 
Published: April 2017

AbstractThe Tb1−xYxMn2Ge2 series (x = 0, 0.1, 0.2) compounds are found to exhibit two magnetic phase transitions with decreasing temperature: from the paramagnetic state to the antiferromagnetic interlayer state at TNinter and from an antiferromagnetic interlayer structure to a collinear ferrimagnetic interlayer structure at TCinter. Compared with the slight change of TNinter (409 K, 410 K and 417 K for x = 0, 0.1 and 0.2 respectively), the replacement of Y for Tb leads to a significant decrease in TCinter from 97.5 K for x = 0 to 74.6 K for x = 0.2. The variation in TCinter can be ascribed to the combination of two effects: (1) chemical pressure and (2) magnetic dilution effect by Y substitution for Tb. Besides, a strong anisotropic magnet-volume effect has been detected around TCinter in all compounds with Δa/a = 0.125%, 0.124% and 0.130% for x = 0, 0.1 and 0.2, respectively while no obvious effect is detected along the c-axis. The maximum magnetic entropy change were found to be −ΔSmax = 9.1 J kg−1 K−1, 11.9 J kg−1 K−1 and 6.3 J kg−1 K−1 with a field change from 0 T to 5 T for x = 0, 0.1, 0.2 respectively.
Natural Scales in Geographical Patterns
Authors: Menezes Telmo , Roth Camille 
Published: April 2017

AbstractHuman mobility is known to be distributed across several orders of magnitude of physical distances, which makes it generally difficult to endogenously find or define typical and meaningful scales. Relevant analyses, from movements to geographical partitions, seem to be relative to some ad-hoc scale, or no scale at all. Relying on geotagged data collected from photo-sharing social media, we apply community detection to movement networks constrained by increasing percentiles of the distance distribution. Using a simple parameter-free discontinuity detection algorithm, we discover clear phase transitions in the community partition space. The detection of these phases constitutes the first objective method of characterising endogenous, natural scales of human movement. Our study covers nine regions, ranging from cities to countries of various sizes and a transnational area. For all regions, the number of natural scales is remarkably low (2 or 3). Further, our results hint at scale-related behaviours rather than scale-related users. The partitions of the natural scales allow us to draw discrete multi-scale geographical boundaries, potentially capable of providing key insights in fields such as epidemiology or cultural contagion where the introduction of spatial boundaries is pivotal.
Crosstalk between signals initiated from TLR4 and cell surface BAFF results in synergistic induction of proinflammatory mediators in THP-1 cells
Authors: Lim Su-Geun , Kim Jae-Kwan , Suk Kyoungho , Lee Won-Ha 
Published: April 2017

AbstractCellular response to stimulation is mediated by meshwork of signaling pathways that may share common signaling adaptors. Here, we present data demonstrating that signaling pathways initiated from the membrane-bound form of B-cell activating factor (BAFF) can crosstalk with lipopolysaccharide (LPS)-induced signaling for synergistic expression of proinflammatory mediators in the human macrophage-like cell line THP-1. Co-treatment of the cells with BAFF-specific monoclonal antibody and LPS resulted in enhanced mitogen-activated protein kinase (MAPK)/mitogen- and stress-activated protein kinase (MSK)-mediated phosphorylation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p65 subunit (Ser276), which then interacts with CREB binding protein (CBP) for subsequent acetylation. Simultaneously, the phosphorylation of cyclic AMP-response element binding protein (CREB) was enhanced through the combined action of phosphatidylinositol-3-kinase (PI3K)/AKT and MAPK/MSK pathways, and the resulting phospho-CREB interacted with the NF-κB/CBP complex. Transfection of CREB-specific siRNA inhibited the BAFF-mediated enhancing effect indicating that the formation of the CREB/NF-κB/CBP complex is required for the synergistic induction of the proinflammatory genes. These findings indicate that BAFF-mediated reverse signaling can modulate LPS-induced inflammatory activation through regulation of NF-κB and CREB activity and point out the necessity to re-evaluate the role of BAFF in diseases where its expression is high in macrophages.