bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single cell RNA sequencing of human liver reveals distinct intrahepatic macrophage populations
Authors: MacParland Sonya A. , Liu Jeff C. , Ma Xue-Zhong , Innes Brendan T. , Bartczak Agata M. , Gage Blair K. , Manuel Justin , Khuu Nicholas , Echeverri Juan , Linares Ivan , Gupta Rahul , Cheng Michael L. , Liu Lewis Y. , Camat Damra , Chung Sai W. , Seliga Rebecca K. , Shao Zigong , Lee Elizabeth , Ogawa Shinichiro , Ogawa Mina , Wilson Michael D. , Fish Jason E. , Selzner Markus , Ghanekar Anand , Grant David , Greig Paul , Sapisochin Gonzalo , Selzner Nazia , Winegarden Neil , Adeyi Oyedele , Keller Gordon , Bader Gary D. , McGilvray Ian D. 
Published: October 2018

AbstractThe liver is the largest solid organ in the body and is critical for metabolic and immune functions. However, little is known about the cells that make up the human liver and its immune microenvironment. Here we report a map of the cellular landscape of the human liver using single-cell RNA sequencing. We provide the transcriptional profiles of 8444 parenchymal and non-parenchymal cells obtained from the fractionation of fresh hepatic tissue from five human livers. Using gene expression patterns, flow cytometry, and immunohistochemical examinations, we identify 20 discrete cell populations of hepatocytes, endothelial cells, cholangiocytes, hepatic stellate cells, B cells, conventional and non-conventional T cells, NK-like cells, and distinct intrahepatic monocyte/macrophage populations. Together, our study presents a comprehensive view of the human liver at single-cell resolution that outlines the characteristics of resident cells in the liver, and in particular provides a map of the human hepatic immune microenvironment.
Spherical neutron polarimetry under high pressure for a multiferroic delafossite ferrite
Authors: Terada Noriki , Qureshi Navid , Chapon Laurent C. , Osakabe Toyotaka 
Published: October 2018

AbstractThe analysis of three-dimensional neutron spin polarization vectors, using a technique referred to as spherical neutron polarimetry (SNP), is a very powerful means of determining complex magnetic structures in magnetic materials. However, the requirement to maintain neutrons in a highly polarized state has made it difficult to use this technique in conjunction with extreme experimental conditions. We have developed a high pressure cell made completely of nonmagnetic materials and having no effect on neutron polarizations. Herein, we report the first SNP analyses under high pressure up to 4.0 GPa in the magnetoelectric multiferroic delafossite CuFeO2. This study also determined the complex spiral magnetic structures in these pressure-induced phases, by measuring the full neutron polarization matrix. The results presented herein demonstrate that the SNP measurements are feasible under high pressure conditions, and that this method is a useful approach to study pressure-induced physical phenomena.
3D virtual reconstruction of the Kebara 2 Neandertal thorax
Authors: Gómez-Olivencia Asier , Barash Alon , García-Martínez Daniel , Arlegi Mikel , Kramer Patricia , Bastir Markus , Been Ella 
Published: October 2018

AbstractThe size and shape of the Neandertal thorax has been debated since the first discovery of Neandertal ribs more than 150 years ago, with workers proposing different interpretations ranging from a Neandertal thoracic morphology that is indistinguishable from modern humans, to one that was significantly different from them. Here, we provide a virtual 3D reconstruction of the thorax of the adult male Kebara 2 Neandertal. Our analyses reveal that the Kebara 2 thorax is significantly different but not larger from that of modern humans, wider in its lower segment, which parallels his wide bi-iliac breadth, and with a more invaginated vertebral column. Kinematic analyses show that rib cages that are wider in their lower segment produce greater overall size increments (respiratory capacity) during inspiration. We hypothesize that Neandertals may have had a subtle, but somewhat different breathing mechanism compared to modern humans.
Engineering protein-protein devices for multilayered regulation of mRNA translation using orthogonal proteases in mammalian cells
Authors: Cella Federica , Wroblewska Liliana , Weiss Ron , Siciliano Velia 
Published: October 2018

AbstractThe development of RNA-encoded regulatory circuits relying on RNA-binding proteins (RBPs) has enhanced the applicability and prospects of post-transcriptional synthetic network for reprogramming cellular functions. However, the construction of RNA-encoded multilayer networks is still limited by the availability of composable and orthogonal regulatory devices. Here, we report on control of mRNA translation with newly engineered RBPs regulated by viral proteases in mammalian cells. By combining post-transcriptional and post-translational control, we expand the operational landscape of RNA-encoded genetic circuits with a set of regulatory devices including: i) RBP-protease, ii) protease-RBP, iii) protease–protease, iv) protein sensor protease-RBP, and v) miRNA-protease/RBP interactions. The rational design of protease-regulated proteins provides a diverse toolbox for synthetic circuit regulation that enhances multi-input information processing-actuation of cellular responses. Our approach enables design of artificial circuits that can reprogram cellular function with potential benefits as research tools and for future in vivo therapeutics and biotechnological applications.
Imaging neural activity in the ventral nerve cord of behaving adult Drosophila
Authors: Chen Chin-Lin , Hermans Laura , Viswanathan Meera C. , Fortun Denis , Aymanns Florian , Unser Michael , Cammarato Anthony , Dickinson Michael H. , Ramdya Pavan 
Published: October 2018

AbstractTo understand neural circuits that control limbs, one must measure their activity during behavior. Until now this goal has been challenging, because limb premotor and motor circuits have been largely inaccessible for large-scale recordings in intact, moving animals—a constraint that is true for both vertebrate and invertebrate models. Here, we introduce a method for 2-photon functional imaging from the ventral nerve cord (VNC) of behaving adult Drosophila melanogaster. We use this method to reveal patterns of activity across nerve cord populations during grooming and walking and to uncover the functional encoding of moonwalker ascending neurons (MANs), moonwalker descending neurons (MDNs), and a previously uncharacterized class of locomotion-associated A1 descending neurons. Finally, we develop a genetic reagent to destroy the indirect flight muscles and to facilitate experimental access to the VNC. Taken together, these approaches enable the direct investigation of circuits associated with complex limb movements.
A distinct isoform of ZNF207 controls self-renewal and pluripotency of human embryonic stem cells
Authors: Fang Fang , Xia Ninuo , Angulo Benjamin , Carey Joseph , Cady Zackery , Durruthy-Durruthy Jens , Bennett Theo , Sebastiano Vittorio , Reijo Pera Renee A. 
Published: October 2018

AbstractSelf-renewal and pluripotency in human embryonic stem cells (hESCs) depends upon the function of a remarkably small number of master transcription factors (TFs) that include OCT4, SOX2, and NANOG. Endogenous factors that regulate and maintain the expression of master TFs in hESCs remain largely unknown and/or uncharacterized. Here, we use a genome-wide, proteomics approach to identify proteins associated with the OCT4 enhancer. We identify known OCT4 regulators, plus a subset of potential regulators including a zinc finger protein, ZNF207, that plays diverse roles during development. In hESCs, ZNF207 partners with master pluripotency TFs to govern self-renewal and pluripotency while simultaneously controlling commitment of cells towards ectoderm through direct regulation of neuronal TFs, including OTX2. The distinct roles of ZNF207 during differentiation occur via isoform switching. Thus, a distinct isoform of ZNF207 functions in hESCs at the nexus that balances pluripotency and differentiation to ectoderm.
Genome organization and DNA accessibility control antigenic variation in trypanosomes
Authors: Müller Laura S. M. , Cosentino Raúl O. , Förstner Konrad U. , Guizetti Julien , Wedel Carolin , Kaplan Noam , Janzen Christian J. , Arampatzi Panagiota , Vogel Jörg , Steinbiss Sascha , Otto Thomas D. , Saliba Antoine-Emmanuel , Sebra Robert P. , Siegel T. Nicolai 
Published: October 2018

AbstractMany evolutionarily distant pathogenic organisms have evolved similar survival strategies to evade the immune responses of their hosts. These include antigenic variation, through which an infecting organism prevents clearance by periodically altering the identity of proteins that are visible to the immune system of the host1. Antigenic variation requires large reservoirs of immunologically diverse antigen genes, which are often generated through homologous recombination, as well as mechanisms to ensure the expression of one or very few antigens at any given time. Both homologous recombination and gene expression are affected by three-dimensional genome architecture and local DNA accessibility2,3. Factors that link three-dimensional genome architecture, local chromatin conformation and antigenic variation have, to our knowledge, not yet been identified in any organism. One of the major obstacles to studying the role of genome architecture in antigenic variation has been the highly repetitive nature and heterozygosity of antigen-gene arrays, which has precluded complete genome assembly in many pathogens. Here we report the de novo haplotype-specific assembly and scaffolding of the long antigen-gene arrays of the model protozoan parasite Trypanosoma brucei, using long-read sequencing technology and conserved features of chromosome folding4. Genome-wide chromosome conformation capture (Hi-C) reveals a distinct partitioning of the genome, with antigen-encoding subtelomeric regions that are folded into distinct, highly compact compartments. In addition, we performed a range of analyses—Hi-C, fluorescence in situ hybridization, assays for transposase-accessible chromatin using sequencing and single-cell RNA sequencing—that showed that deletion of the histone variants H3.V and H4.V increases antigen-gene clustering, DNA accessibility across sites of antigen expression and switching of the expressed antigen isoform, via homologous recombination. Our analyses identify histone variants as a molecular link between global genome architecture, local chromatin conformation and antigenic variation.
Tryptophan 32-mediated SOD1 aggregation is attenuated by pyrimidine-like compounds in living cells
Authors: Pokrishevsky Edward , McAlary Luke , Farrawell Natalie E. , Zhao Beibei , Sher Mine , Yerbury Justin J. , Cashman Neil R. 
Published: October 2018

AbstractOver 160 mutations in superoxide dismutase 1 (SOD1) are associated with familial amyotrophic lateral sclerosis (fALS), where the main pathological feature is deposition of SOD1 into proteinaceous cytoplasmic inclusions. We previously showed that the tryptophan residue at position 32 (W32) mediates the prion-like propagation of SOD1 misfolding in cells, and that a W32S substitution blocks this phenomenon. Here, we used in vitro protein assays to demonstrate that a W32S substitution in SOD1-fALS mutants significantly diminishes their propensity to aggregate whilst paradoxically decreasing protein stability. We also show SOD1-W32S to be resistant to seeded aggregation, despite its high abundance of unfolded protein. A cell-based aggregation assay demonstrates that W32S substitution significantly mitigates inclusion formation. Furthermore, this assay reveals that W32 in SOD1 is necessary for the formation of a competent seed for aggregation under these experimental conditions. Following the observed importance of W32 for aggregation, we established that treatment of living cells with the W32-interacting 5-Fluorouridine (5-FUrd), and its FDA approved analogue 5-Fluorouracil (5-FU), substantially attenuate inclusion formation similarly to W32S substitution. Altogether, we highlight W32 as a significant contributor to SOD1 aggregation, and propose that 5-FUrd and 5-FU present promising lead drug candidates for the treatment of SOD1-associated ALS.
Simultaneous Digital Design and Additive Manufacture of Structures and Materials
Authors: Boddeti Narasimha , Ding Zhen , Kaijima Sawako , Maute Kurt , Dunn Martin L. 
Published: October 2018

AbstractThe integration of emerging technologies into a complete digital thread promises to disrupt design and manufacturing workflows throughout the value chain to enable efficiency and productivity transformation, while unlocking completely new design freedom. A particularly appealing aspect involves the simultaneous design and manufacture of the macroscale structural topology and material microstructure of a product. Here we demonstrate such a workflow that digitally integrates: design automation – conception and automation of a design problem based on multiscale topology optimization; material compilation – computational geometry algorithms that create spatially-variable, physically-realizable multimaterial microstructures; and digital fabrication – fabrication of multiscale optimized components via voxel-based additive manufacturing with material jetting of multiple photo-curable polymers. We validate the digital design and manufacturing workflow by designing, fabricating, and testing a series of structures that illustrate capabilities, show how it empowers the exploitation of new design freedom, and even challenges traditional design principles relating form, structure, and function.
The impact of drainage displacement patterns and Haines jumps on CO2 storage efficiency
Authors: Zacharoudiou Ioannis , Boek Edo S. , Crawshaw John 
Published: October 2018

AbstractInjection of CO2 deep underground into porous rocks, such as saline aquifers, appears to be a promising tool for reducing CO2 emissions and the consequent climate change. During this process CO2 displaces brine from individual pores and the sequence in which this happens determines the efficiency with which the rock is filled with CO2 at the large scale. At the pore scale, displacements are controlled by the balance of capillary, viscous and inertial forces. We simulate this process by a numerical technique, multi-GPU Lattice Boltzmann, using X-ray images of the rock pores. The simulations show the three types of fluid displacement patterns, at the larger scale, that have been previously observed in both experiments and simulations: viscous fingering, capillary fingering and stable displacement. Here we examine the impact of the patterns on storage efficiency and then focus on slow flows, where displacements at the pore scale typically happen by sudden jumps in the position of the interface between brine and CO2, Haines jumps. During these jumps, the fluid in surrounding pores can rearrange in a way that prevent later displacements in nearby pores, potentially reducing the efficiency with which the CO2 fills the total available volume in the rock.
Quasi-Spatially Periodic Signals for Optical Fibre Communications
Authors: Zhang Qun , Chan Terence H. , Grant Alex 
Published: October 2018

AbstractWe study quasi-spatially periodic signals (QSPSs) as a class of input signals of interest, which maintain their shapes quasi-periodically (with a phase change and a time shift) during propagation in an optical fibre. Instead of the computationally expensive nonlinear Fourier transform (NFT), the property of quasi-periodic shape invariant could be used as an alternative for decoding at the receiver. In this paper, properties of QSPSs and the signal design problem are studied, including the trade-off between various system parameters.
Low abundance of sharks and rays in baited remote underwater video surveys in the Arabian Gulf
Authors: Jabado Rima W. , Al Hameli Shamsa M. , Grandcourt Edwin M. , Al Dhaheri Shaikha S. 
Published: October 2018

AbstractData on the diversity and relative abundance of elasmobranchs (sharks and rays) in the Arabian Gulf have been limited to fishery-dependent monitoring of landing sites. Understanding the diversity and abundance of sharks and rays is, however, crucial to inform policy and management plans. Baited Remote Underwater Video Surveys (BRUVS) were conducted in 2015–2016 across the United Arab Emirates Arabian Gulf waters encompassing a range of depths and habitat types. Data from 278 BRUVS (757 hours soak time) were analysed to gather information on diversity, relative abundance, species distribution, and habitat associations. Surveys recorded 213 individuals from 20 species of sharks and rays at 129 stations. The frequency of occurrence of species usually discarded by fishers such as the Arabian carpetshark (Chiloscyllium arabicum) and stingrays (Himantura spp.) was high, accounting for 60.5% of observed elasmobranchs. Despite the large survey area covered and extensive sampling effort, the relative abundance of sharks and rays was low at 0.28 elasmobranchs per hour, 0.13 sharks per hour, and 0.15 rays per hour. This CPUE was reduced to one of lowest recorded abundance on BRUVS from around the world when removing the two discarded species from the analysis (0.11 elasmobranchs per hour). These results likely reflect the intense fishing pressure and habitat loss contributing to population declines of many elasmobranchs in the Arabian Gulf. Findings provide a baseline for future work and can support the design of conservation strategies for sharks and rays in the UAE.
LncRNA BLAT1 is Upregulated in Basal-like Breast Cancer through Epigenetic Modifications
Authors: Han Yoo Jane , Boatman Sonja M. , Zhang Jing , Du Xinxin C. , Yeh Albert C. , Zheng Yonglan , Mueller Jeffrey , Olopade Olufunmilayo I. 
Published: October 2018

AbstractLong-noncoding RNAs (lncRNAs) have been shown to participate in oncogenesis across a variety of cancers and may represent novel therapeutic targets. However, little is known about the role of lncRNAs in basal-like breast cancer (BLBC), the aggressive form of breast cancer with no molecularly defined therapeutic target. To examine whether altered lncRNA expression contributes to the aggressive phenotype characteristic of BLBC, we performed a comparative analysis of BLBC versus non-BLBC using microarray profiling and RNA sequencing of primary breast cancer. We identified RP11-19E11.1 as a significantly up-regulated lncRNA in BLBC tumors and named it Basal-Like breast cancer Associated Transcript 1 (BLAT1). Analysis of pan-cancer datasets showed the highest expression of BLAT1 in BLBC tumors compared to all other cancers. Depletion of BLAT1 in breast cancer cells led to significantly increased apoptosis, partly because of accumulation of DNA damage. Mechanistically, BLAT1 expression is regulated at the epigenetic level via DNA methylation at CpG islands in the promoter. Concordantly, patients harboring tumors with BLAT1 hypomethylation showed decreased overall survival. Our results suggest that increased expression of BLAT1 via CpG site hypomethylation may contribute to the aggressive phenotype of BLBC, raising a possibility of new biomarkers for prognosis of aggressive BLBC tumors.
Three-dimensional tracking of microbeads attached to the tip of single isolated tracheal cilia beating under external load
Authors: Katoh Takanobu A. , Ikegami Koji , Uchida Nariya , Iwase Toshihito , Nakane Daisuke , Masaike Tomoko , Setou Mitsutoshi , Nishizaka Takayuki 
Published: October 2018

AbstractTo study the properties of tracheal cilia beating under various conditions, we developed a method to monitor the movement of the ciliary tip. One end of a demembranated cilium was immobilized on the glass surface, while the other end was capped with a polystyrene bead and tracked in three dimensions. The cilium, when activated by ATP, stably repeated asymmetric beating as in vivo. The tip of a cilium in effective and recovery strokes moved in discrete trajectories that differed in height. The trajectory remained asymmetric in highly viscous solutions. Model calculation showed that cilia maintained a constant net flux during one beat cycle irrespective of the medium viscosity. When the bead attached to the end was trapped with optical tweezers, it came to display linear oscillation only in the longitudinal direction. Such a beating-mode transition may be an inherent nature of movement-restricted cilia.
High-resolution isotopic evidence for a potential Saharan provenance of Greenland glacial dust
Authors: Han Changhee , Do Hur Soon , Han Yeongcheol , Lee Khanghyun , Hong Sungmin , Erhardt Tobias , Fischer Hubertus , Svensson Anders M. , Steffensen Jørgen Peder , Vallelonga Paul 
Published: October 2018

AbstractDust concentrations in Greenland ice show pronounced glacial/interglacial variations with almost two orders of magnitude increase during the Last Glacial Maximum. Greenland glacial dust was previously sourced to two East Asian deserts: the Taklimakan and Gobi deserts. Here we report the first high-resolution Pb and Sr isotopic evidence for a significant Saharan dust influence in Greenland during the last glacial period, back to ~31 kyr ago, from the Greenland NEEM ice core. We find that during Greenland Stadials 3–5.1 (~31 to 23 kyr ago), the primary dust provenance was East Asia, as previously proposed. Subsequently, the Saharan isotopic signals emerge during Greenland Stadials 2.1a–2.1c (~22.6 to 14.7 kyr ago) and from the late Bølling-Allerød to the Younger Dryas periods (~13.6 to 12 kyr ago), coincident with increased aridity in the Sahara and efficient northward transport of dust during these cold periods. A mixing isotopic model proposes the Sahara as an important source, accounting for contribution to Greenland glacial dust of up to 50%, particularly during Greenland Stadial 2.1b and the late Bølling-Allerød to the Younger Dryas periods. Our findings provide new insights into climate-related dust provenance changes and essential paleoclimatic constraints on dust-climate feedbacks in northern high latitudes.
A comparison of inverted and upright laser-activated titanium nitride micropyramids for intracellular delivery
Authors: Raun Alexander , Saklayen Nabiha , Zgrabik Christine , Shen Weilu , Madrid Marinna , Huber Marinus , Hu Evelyn , Mazur Eric 
Published: October 2018

AbstractThe delivery of biomolecules into cells relies on porating the plasma membrane to allow exterior molecules to enter the cell via diffusion. Various established delivery methods, including electroporation and viral techniques, come with drawbacks such as low viability or immunotoxicity, respectively. An optics-based delivery method that uses laser pulses to excite plasmonic titanium nitride (TiN) micropyramids presents an opportunity to overcome these shortcomings. This laser excitation generates localized nano-scale heating effects and bubbles, which produce transient pores in the cell membrane for payload entry. TiN is a promising plasmonic material due to its high hardness and thermal stability. In this study, two designs of TiN micropyramid arrays are constructed and tested. These designs include inverted and upright pyramid structures, each coated with a 50-nm layer of TiN. Simulation software shows that the inverted and upright designs reach temperatures of 875 °C and 307 °C, respectively, upon laser irradiation. Collectively, experimental results show that these reusable designs achieve maximum cell poration efficiency greater than 80% and viability greater than 90% when delivering calcein dye to target cells. Overall, we demonstrate that TiN microstructures are strong candidates for future use in biomedical devices for intracellular delivery and regenerative medicine.