bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ultra-fast vortex motion in a direct-write Nb-C superconductor
Authors: Dobrovolskiy O. V. , Vodolazov D. Yu , Porrati F. , Sachser R. , Bevz V. M. , Mikhailov M. Yu , Chumak A. V. , Huth M. 
Published: July 2020

AbstractThe ultra-fast dynamics of superconducting vortices harbors rich physics generic to nonequilibrium collective systems. The phenomenon of flux-flow instability (FFI), however, prevents its exploration and sets practical limits for the use of vortices in various applications. To suppress the FFI, a superconductor should exhibit a rarely achieved combination of properties: weak volume pinning, close-to-depairing critical current, and fast heat removal from heated electrons. Here, we demonstrate experimentally ultra-fast vortex motion at velocities of 10–15 km s−1 in a directly written Nb-C superconductor with a close-to-perfect edge barrier. The spatial evolution of the FFI is described using the edge-controlled FFI model, implying a chain of FFI nucleation points along the sample edge and their development into self-organized Josephson-like junctions (vortex rivers). In addition, our results offer insights into the applicability of widely used FFI models and suggest Nb-C to be a good candidate material for fast single-photon detectors.
TMEM16K is an interorganelle regulator of endosomal sorting
Authors: Petkovic Maja , Oses-Prieto Juan , Burlingame Alma , Jan Lily Yeh , Jan Yuh Nung 
Published: July 2020

AbstractCommunication between organelles is essential for their cellular homeostasis. Neurodegeneration reflects the declining ability of neurons to maintain cellular homeostasis over a lifetime, where the endolysosomal pathway plays a prominent role by regulating protein and lipid sorting and degradation. Here we report that TMEM16K, an endoplasmic reticulum lipid scramblase causative for spinocerebellar ataxia (SCAR10), is an interorganelle regulator of the endolysosomal pathway. We identify endosomal transport as a major functional cluster of TMEM16K in proximity biotinylation proteomics analyses. TMEM16K forms contact sites with endosomes, reconstituting split-GFP with the small GTPase RAB7. Our study further implicates TMEM16K lipid scrambling activity in endosomal sorting at these sites. Loss of TMEM16K function led to impaired endosomal retrograde transport and neuromuscular function, one of the symptoms of SCAR10. Thus, TMEM16K-containing ER-endosome contact sites represent clinically relevant platforms for regulating endosomal sorting.
Subsurface chemical nanoidentification by nano-FTIR spectroscopy
Authors: Mester Lars , Govyadinov Alexander A. , Chen Shu , Goikoetxea Monika , Hillenbrand Rainer 
Published: July 2020

AbstractNano-FTIR spectroscopy based on Fourier transform infrared near-field spectroscopy allows for label-free chemical nanocharacterization of organic and inorganic composite surfaces. The potential capability for subsurface material analysis, however, is largely unexplored terrain. Here, we demonstrate nano-FTIR spectroscopy of subsurface organic layers, revealing that nano-FTIR spectra from thin surface layers differ from that of subsurface layers of the same organic material. Further, we study the correlation of various nano-FTIR peak characteristics and establish a simple and robust method for distinguishing surface from subsurface layers without the need of theoretical modeling or simulations (provided that chemically induced spectral modifications are not present). Our experimental findings are confirmed and explained by a semi-analytical model for calculating nano-FTIR spectra of multilayered organic samples. Our results are critically important for the interpretation of nano-FTIR spectra of multilayer samples, particularly to avoid that geometry-induced spectral peak shifts are explained by chemical effects.
Transcriptomic and cellular decoding of regional brain vulnerability to neurogenetic disorders
Authors: Seidlitz Jakob , Nadig Ajay , Liu Siyuan , Bethlehem Richard A. I. , Vértes Petra E. , Morgan Sarah E. , Váša František , Romero-Garcia Rafael , Lalonde François M. , Clasen Liv S. , Blumenthal Jonathan D. , Paquola Casey , Bernhardt Boris , Wagstyl Konrad , Polioudakis Damon , de la Torre-Ubieta Luis , Geschwind Daniel H. , Han Joan C. , Lee Nancy R. , Murphy Declan G. , Bullmore Edward T. , Raznahan Armin 
Published: July 2020

AbstractNeurodevelopmental disorders have a heritable component and are associated with region specific alterations in brain anatomy. However, it is unclear how genetic risks for neurodevelopmental disorders are translated into spatially patterned brain vulnerabilities. Here, we integrated cortical neuroimaging data from patients with neurodevelopmental disorders caused by genomic copy number variations (CNVs) and gene expression data from healthy subjects. For each of the six investigated disorders, we show that spatial patterns of cortical anatomy changes in youth are correlated with cortical spatial expression of CNV genes in neurotypical adults. By transforming normative bulk-tissue cortical expression data into cell-type expression maps, we link anatomical change maps in each analysed disorder to specific cell classes as well as the CNV-region genes they express. Our findings reveal organizing principles that regulate the mapping of genetic risks onto regional brain changes in neurogenetic disorders. Our findings will enable screening for candidate molecular mechanisms from readily available neuroimaging data.
Butyrate producing colonic Clostridiales metabolise human milk oligosaccharides and cross feed on mucin via conserved pathways
Authors: Pichler Michael Jakob , Yamada Chihaya , Shuoker Bashar , Alvarez-Silva Camila , Gotoh Aina , Leth Maria Louise , Schoof Erwin , Katoh Toshihiko , Sakanaka Mikiyasu , Katayama Takane , Jin Chunsheng , Karlsson Niclas G. , Arumugam Manimozhiyan , Fushinobu Shinya , Abou Hachem Maher 
Published: July 2020

AbstractThe early life human gut microbiota exerts life-long health effects on the host, but the mechanisms underpinning its assembly remain elusive. Particularly, the early colonization of Clostridiales from the Roseburia-Eubacterium group, associated with protection from colorectal cancer, immune- and metabolic disorders is enigmatic. Here, we describe catabolic pathways that support the growth of Roseburia and Eubacterium members on distinct human milk oligosaccharides (HMOs). The HMO pathways, which include enzymes with a previously unknown structural fold and specificity, were upregulated together with additional glycan-utilization loci during growth on selected HMOs and in co-cultures with Akkermansia muciniphila on mucin, suggesting an additional role in enabling cross-feeding and access to mucin O-glycans. Analyses of 4599 Roseburia genomes underscored the preponderance and diversity of the HMO utilization loci within the genus. The catabolism of HMOs by butyrate-producing Clostridiales may contribute to the competitiveness of this group during the weaning-triggered maturation of the microbiota.
Mapping effector genes at lupus GWAS loci using promoter Capture-C in follicular helper T cells
Authors: Su Chun , Johnson Matthew E. , Torres Annabel , Thomas Rajan M. , Manduchi Elisabetta , Sharma Prabhat , Mehra Parul , Le Coz Carole , Leonard Michelle E. , Lu Sumei , Hodge Kenyaita M. , Chesi Alessandra , Pippin James , Romberg Neil , Grant Struan F. A. , Wells Andrew D. 
Published: July 2020

AbstractSystemic lupus erythematosus (SLE) is mediated by autoreactive antibodies that damage multiple tissues. Genome-wide association studies (GWAS) link >60 loci with SLE risk, but the causal variants and effector genes are largely unknown. We generated high-resolution spatial maps of SLE variant accessibility and gene connectivity in human follicular helper T cells (TFH), a cell type required for anti-nuclear antibodies characteristic of SLE. Of the ~400 potential regulatory variants identified, 90% exhibit spatial proximity to genes distant in the 1D genome sequence, including variants that loop to regulate the canonical TFH genes BCL6 and CXCR5 as confirmed by genome editing. SLE ‘variant-to-gene’ maps also implicate genes with no known role in TFH/SLE disease biology, including the kinases HIPK1 and MINK1. Targeting these kinases in TFH inhibits production of IL-21, a cytokine crucial for class-switched B cell antibodies. These studies offer mechanistic insight into the SLE-associated regulatory architecture of the human genome.
Diamond Blackfan anemia is mediated by hyperactive Nemo-like kinase
Authors: Wilkes M. C. , Siva K. , Chen J. , Varetti G. , Youn M. Y. , Chae H. , Ek F. , Olsson R. , Lundbäck T. , Dever D. P. , Nishimura T. , Narla A. , Glader B. , Nakauchi H. , Porteus M. H. , Repellin C. E. , Gazda H. T. , Lin S. , Serrano M. , Flygare J. , Sakamoto K. M. 
Published: July 2020

AbstractDiamond Blackfan Anemia (DBA) is a congenital bone marrow failure syndrome associated with ribosomal gene mutations that lead to ribosomal insufficiency. DBA is characterized by anemia, congenital anomalies, and cancer predisposition. Treatment for DBA is associated with significant morbidity. Here, we report the identification of Nemo-like kinase (NLK) as a potential target for DBA therapy. To identify new DBA targets, we screen for small molecules that increase erythroid expansion in mouse models of DBA. This screen identified a compound that inhibits NLK. Chemical and genetic inhibition of NLK increases erythroid expansion in mouse and human progenitors, including bone marrow cells from DBA patients. In DBA models and patient samples, aberrant NLK activation is initiated at the Megakaryocyte/Erythroid Progenitor (MEP) stage of differentiation and is not observed in non-erythroid hematopoietic lineages or healthy erythroblasts. We propose that NLK mediates aberrant erythropoiesis in DBA and is a potential target for therapy.
Low thermal conductivity of iron-silicon alloys at Earth’s core conditions with implications for the geodynamo
Authors: Hsieh Wen-Pin , Goncharov Alexander F. , Labrosse Stéphane , Holtgrewe Nicholas , Lobanov Sergey S. , Chuvashova Irina , Deschamps Frédéric , Lin Jung-Fu 
Published: July 2020

AbstractEarth’s core is composed of iron (Fe) alloyed with light elements, e.g., silicon (Si). Its thermal conductivity critically affects Earth’s thermal structure, evolution, and dynamics, as it controls the magnitude of thermal and compositional sources required to sustain a geodynamo over Earth’s history. Here we directly measured thermal conductivities of solid Fe and Fe–Si alloys up to 144 GPa and 3300 K. 15 at% Si alloyed in Fe substantially reduces its conductivity by about 2 folds at 132 GPa and 3000 K. An outer core with 15 at% Si would have a conductivity of about 20 W m−1 K−1, lower than pure Fe at similar pressure–temperature conditions. This suggests a lower minimum heat flow, around 3 TW, across the core–mantle boundary than previously expected, and thus less thermal energy needed to operate the geodynamo. Our results provide key constraints on inner core age that could be older than two billion-years.
Polymer physics indicates chromatin folding variability across single-cells results from state degeneracy in phase separation
Authors: Conte Mattia , Fiorillo Luca , Bianco Simona , Chiariello Andrea M. , Esposito Andrea , Nicodemi Mario 
Published: July 2020

AbstractThe spatial organization of chromosomes has key functional roles, yet how chromosomes fold remains poorly understood at the single-molecule level. Here, we employ models of polymer physics to investigate DNA loci in human HCT116 and IMR90 wild-type and cohesin depleted cells. Model predictions on single-molecule structures are validated against single-cell imaging data, providing evidence that chromosomal architecture is controlled by a thermodynamics mechanism of polymer phase separation whereby chromatin self-assembles in segregated globules by combinatorial interactions of chromatin factors that include CTCF and cohesin. The thermodynamics degeneracy of single-molecule conformations results in broad structural and temporal variability of TAD-like contact patterns. Globules establish stable environments where specific contacts are highly favored over stochastic encounters. Cohesin depletion reverses phase separation into randomly folded states, erasing average interaction patterns. Overall, globule phase separation appears to be a robust yet reversible mechanism of chromatin organization where stochasticity and specificity coexist.
A sequential methodology for the rapid identification and characterization of breast cancer-associated functional SNPs
Authors: Zhao Yihan , Wu Di , Jiang Danli , Zhang Xiaoyu , Wu Ting , Cui Jing , Qian Min , Zhao Jean , Oesterreich Steffi , Sun Wei , Finkel Toren , Li Gang 
Published: July 2020

AbstractGWAS cannot identify functional SNPs (fSNP) from disease-associated SNPs in linkage disequilibrium (LD). Here, we report developing three sequential methodologies including Reel-seq (Regulatory element-sequencing) to identify fSNPs in a high-throughput fashion, SDCP-MS (SNP-specific DNA competition pulldown-mass spectrometry) to identify fSNP-bound proteins and AIDP-Wb (allele-imbalanced DNA pulldown-Western blot) to detect allele-specific protein:fSNP binding. We first apply Reel-seq to screen a library containing 4316 breast cancer-associated SNPs and identify 521 candidate fSNPs. As proof of principle, we verify candidate fSNPs on three well-characterized loci: FGFR2, MAP3K1 and BABAM1. Next, using SDCP-MS and AIDP-Wb, we rapidly identify multiple regulatory factors that specifically bind in an allele-imbalanced manner to the fSNPs on the FGFR2 locus. We finally demonstrate that the factors identified by SDCP-MS can regulate risk gene expression. These data suggest that the sequential application of Reel-seq, SDCP-MS, and AIDP-Wb can greatly help to translate large sets of GWAS data into biologically relevant information.
Collective dipole effects in ionic transport under electric fields
Authors: Salles N. , Martin-Samos L. , de Gironcoli S. , Giacomazzi L. , Valant M. , Hemeryck A. , Blaise P. , Sklenard B. , Richard N. 
Published: July 2020

AbstractIn the context of ionic transport in solids, the variation of a migration barrier height under electric fields is traditionally assumed to be equal to the classical electric work of a point charge that carries the transport charge. However, how reliable is this phenomenological model and how does it fare with respect to Modern Theory of Polarization? In this work, we show that such a classical picture does not hold in general as collective dipole effects may be critical. Such effects are unraveled by an appropriate polarization decomposition and by an expression that we derive, which defines the equivalent polarization-work charge. The equivalent polarization-work charge is not equal neither to the transported charge, nor to the Born effective charge of the migrating atom alone, but it is defined by the total polarization change at the transition state. Our findings are illustrated by oxygen charged defects in MgO and in SiO2.
Dietary glutamine supplementation suppresses epigenetically-activated oncogenic pathways to inhibit melanoma tumour growth
Authors: Ishak Gabra Mari B. , Yang Ying , Li Haiqing , Senapati Parijat , Hanse Eric A. , Lowman Xazmin H. , Tran Thai Q. , Zhang Lishi , Doan Linda T. , Xu Xiangdong , Schones Dustin E. , Fruman David A. , Kong Mei 
Published: July 2020

AbstractTumour cells adapt to nutrient deprivation in vivo, yet strategies targeting the nutrient poor microenvironment remain unexplored. In melanoma, tumour cells often experience low glutamine levels, which promote cell dedifferentiation. Here, we show that dietary glutamine supplementation significantly inhibits melanoma tumour growth, prolongs survival in a transgenic melanoma mouse model, and increases sensitivity to a BRAF inhibitor. Metabolomic analysis reveals that dietary uptake of glutamine effectively increases the concentration of glutamine in tumours and its downstream metabolite, αKG, without increasing biosynthetic intermediates necessary for cell proliferation. Mechanistically, we find that glutamine supplementation uniformly alters the transcriptome in tumours. Our data further demonstrate that increase in intra-tumoural αKG concentration drives hypomethylation of H3K4me3, thereby suppressing epigenetically-activated oncogenic pathways in melanoma. Therefore, our findings provide evidence that glutamine supplementation can serve as a potential dietary intervention to block melanoma tumour growth and sensitize tumours to targeted therapy via epigenetic reprogramming.
A Keplerian Ag90 nest of Platonic and Archimedean polyhedra in different symmetry groups
Authors: Su Yan-Min , Wang Zhi , Schein Stan , Tung Chen-Ho , Sun Di 
Published: July 2020

AbstractPolyhedra are ubiquitous in chemistry, biology, mathematics and other disciplines. Coordination-driven self-assembly has created molecules mimicking Platonic, Archimedean and even Goldberg polyhedra, however, nesting multiple polyhedra in one cluster is challenging, not only for synthesis but also for determining the alignment of the polyhedra. Here, we synthesize a nested Ag90 nanocluster under solvothermal condition. This pseudo-Th symmetric Ag90 ball contains three concentric Ag polyhedra with apparently incompatible symmetry. Specifically, the inner (Ag6) and middle (Ag24) shells are octahedral (Oh), an octahedron (a Platonic solid with six 3.3.3.3 vertices) and a truncated octahedron (an Archimedean solid with twenty-four 4.6.6 vertices), whereas the outer (Ag60) shell is icosahedral (Ih), a rhombicosidodecahedron (an Archimedean solid with sixty 3.4.5.4 vertices). The Ag90 nanocluster solves the apparent incompatibility with the most symmetric arrangement of 2- and 3-fold rotational axes, similar to the arrangement in the model called Kepler’s Kosmos, devised by the mathematician John Conway.
Rational flux-tuning of Halomonas bluephagenesis for co-production of bioplastic PHB and ectoine
Authors: Ma Hong , Zhao Yiqing , Huang Wuzhe , Zhang Lizhan , Wu Fuqing , Ye Jianwen , Chen Guo-Qiang 
Published: July 2020

AbstractEctoine, a compatible solute synthesized by many halophiles for hypersalinity resistance, has been successfully produced by metabolically engineeredHalomonas bluephagenesis, which is a bioplastic poly(3-hydroxybutyrate) producer allowing open unsterile and continuous conditions. Here we report a de novo synthesis pathway for ectoine constructed into the chromosome ofH. bluephagenesisutilizing two inducible systems, which serve to fine-tune the transcription levels of three clusters related to ectoine synthesis, includingectABC,lysCandasdbased on a GFP-mediated transcriptional tuning approach. Combined with bypasses deletion, the resulting recombinantH. bluephagenesisTD-ADEL-58 is able to produce 28 g L−1ectoine during a 28 h fed-batch growth process. Co-production of ectoine and PHB is achieved to 8 g L−1ectoine and 32 g L−1dry cell mass containing 75% PHB after a 44 h growth.H. bluephagenesisdemonstrates to be a suitable co-production chassis for polyhydroxyalkanoates and non-polymer chemicals such as ectoine.
Three-terminal Weyl complex with double surface arcs in a cubic lattice
Authors: Huang Zhenqiao , Chen Zhongjia , Zheng Baobing , Xu Hu 
Published: July 2020

AbstractExploring unconventional topological quasiparticles and their associated exotic physical properties has become a hot topic in condensed matter physics, thus stimulating extensive interest in recent years. Here, in contrast to the double-Weyl phonons (the topological chiral charge +2) in the trigonal and hexagonal crystal systems, we propose that the unconventional double-Weyl without counterparts in high-energy physics can emerge in the phonons of cubic structures, i.e., SrSi2. Employing a two-band k ⋅ p Hamiltonian, we prove that the quadratic double-Weyl nodes are protected by the fourfold screw rotational symmetry $${\tilde{C}}_{4}$$

C

̃

4

. Strikingly, we find that the surface arcs are terminated with the Weyl nodes that possess unequal topological charges with opposite sign (i.e., +2 and −1), leading to unique three-terminal Weyl complex (one quadratic double-Weyl and two linear single-Weyl) with double surface arcs in SrSi2. In addition, we apply a uniaxial tensile strain along z-axis to examine the evolution of the three-terminal Weyl complex when the corresponding symmetries are broken. Our work not only provides an ideal candidate for the realization of the quadratic double-Weyl and the corresponding unique surface arc states, but also broadens the understanding of topological Weyl physics.
Probabilistic identification of saccharide moieties in biomolecules and their protein complexes
Authors: Dashti Hesam , Westler William M. , Wedell Jonathan R. , Demler Olga V. , Eghbalnia Hamid R. , Markley John L. , Mora Samia 
Published: July 2020

AbstractThe chemical composition of saccharide complexes underlies their biomedical activities as biomarkers for cardiometabolic disease, various types of cancer, and other conditions. However, because these molecules may undergo major structural modifications, distinguishing between compounds of saccharide and non-saccharide origin becomes a challenging computational problem that hinders the aggregation of information about their bioactive moieties. We have developed an algorithm and software package called “Cheminformatics Tool for Probabilistic Identification of Carbohydrates” (CTPIC) that analyzes the covalent structure of a compound to yield a probabilistic measure for distinguishing saccharides and saccharide-derivatives from non-saccharides. CTPIC analysis of the RCSB Ligand Expo (database of small molecules found to bind proteins in the Protein Data Bank) led to a substantial increase in the number of ligands characterized as saccharides. CTPIC analysis of Protein Data Bank identified 7.7% of the proteins as saccharide-binding. CTPIC is freely available as a webservice at (http://ctpic.nmrfam.wisc.edu).
Resting state functional connectivity of the pain matrix and default mode network in irritable bowel syndrome: a graph theoretical analysis
Authors: Kano Michiko , Grinsvall Cecilia , Ran Qian , Dupont Patrick , Morishita Joe , Muratsubaki Tomohiko , Mugikura Shunji , Ly Huynh Giao , Törnblom Hans , Ljungberg Maria , Takase Kei , Simrén Magnus , Van Oudenhove Lukas , Fukudo Shin 
Published: July 2020

AbstractIrritable bowel syndrome (IBS) is a functional disorder of brain-gut interactions. Differential brain responses to rectal distention between IBS and healthy controls (HCs) have been demonstrated, particularly in the pain matrix and the default mode network. This study aims to compare resting-state functional properties of these networks between IBS patients and HCs using graph analysis in two independent cohorts. We used a weighted graph analysis of the adjacency matrix based on partial correlations between time series in the different regions in each subject to determine subject specific graph measures. These graph measures were normalized by values obtained in equivalent random networks. We did not find any significant differences between IBS patients and controls in global normalized graph measures, hubs, or modularity structure of the pain matrix and the DMN in any of our two independent cohorts. Furthermore, we did not find consistent associations between these global network measures and IBS symptom severity or GI-specific anxiety but we found a significant difference in the relationship between measures of psychological distress (anxiety and/or depressive symptoms) and normalized characteristic path length. The responses of these networks to visceral stimulation rather than their organisation at rest may be primarily disturbed in IBS.