bluuebunny/crossref_metadata_2025_split huggingface dataset:
Brain scans from 21,297 individuals reveal the genetic architecture of hippocampal subfield volumes
Authors:   for the Alzheimer’s Disease Neuroimaging Initiative, van der Meer Dennis ,   for the Pediatric Imaging, Neurocognition and Genetics Study, Rokicki Jaroslav , Kaufmann Tobias , Córdova-Palomera Aldo , Moberget Torgeir , Alnæs Dag , Bettella Francesco , Frei Oleksandr , Doan Nhat Trung , Sønderby Ida E. , Smeland Olav B. , Agartz Ingrid , Bertolino Alessandro , Bralten Janita , Brandt Christine L. , Buitelaar Jan K. , Djurovic Srdjan , van Donkelaar Marjolein , Dørum Erlend S. , Espeseth Thomas , Faraone Stephen V. , Fernández Guillén , Fisher Simon E. , Franke Barbara , Haatveit Beathe , Hartman Catharina A. , Hoekstra Pieter J. , Håberg Asta K. , Jönsson Erik G. , Kolskår Knut K. , Le Hellard Stephanie , Lund Martina J. , Lundervold Astri J. , Lundervold Arvid , Melle Ingrid , Monereo Sánchez Jennifer , Norbom Linn C. , Nordvik Jan E. , Nyberg Lars , Oosterlaan Jaap , Papalino Marco , Papassotiropoulos Andreas , Pergola Giulio , de Quervain Dominique J. F. , Richard Geneviève , Sanders Anne-Marthe , Selvaggi Pierluigi , Shumskaya Elena , Steen Vidar M. , Tønnesen Siren , Ulrichsen Kristine M. , Zwiers Marcel P. , Andreassen Ole A. , Westlye Lars T. 
Published: October 2018

AbstractThe hippocampus is a heterogeneous structure, comprising histologically distinguishable subfields. These subfields are differentially involved in memory consolidation, spatial navigation and pattern separation, complex functions often impaired in individuals with brain disorders characterized by reduced hippocampal volume, including Alzheimer’s disease (AD) and schizophrenia. Given the structural and functional heterogeneity of the hippocampal formation, we sought to characterize the subfields’ genetic architecture. T1-weighted brain scans (n = 21,297, 16 cohorts) were processed with the hippocampal subfields algorithm in FreeSurfer v6.0. We ran a genome-wide association analysis on each subfield, co-varying for whole hippocampal volume. We further calculated the single-nucleotide polymorphism (SNP)-based heritability of 12 subfields, as well as their genetic correlation with each other, with other structural brain features and with AD and schizophrenia. All outcome measures were corrected for age, sex and intracranial volume. We found 15 unique genome-wide significant loci across six subfields, of which eight had not been previously linked to the hippocampus. Top SNPs were mapped to genes associated with neuronal differentiation, locomotor behaviour, schizophrenia and AD. The volumes of all the subfields were estimated to be heritable (h2 from 0.14 to 0.27, all p < 1 × 10–16) and clustered together based on their genetic correlations compared with other structural brain features. There was also evidence of genetic overlap of subicular subfield volumes with schizophrenia. We conclude that hippocampal subfields have partly distinct genetic determinants associated with specific biological processes and traits. Taking into account this specificity may increase our understanding of hippocampal neurobiology and associated pathologies.
Biosynthetic energy cost for amino acids decreases in cancer evolution
Authors: Zhang Hong , Wang Yirong , Li Jun , Chen Han , He Xionglei , Zhang Huiwen , Liang Han , Lu Jian 
Published: October 2018

AbstractRapidly proliferating cancer cells have much higher demand for proteinogenic amino acids than normal cells. The use of amino acids in human proteomes is largely affected by their bioavailability, which is constrained by the biosynthetic energy cost in living organisms. Conceptually distinct from gene-based analyses, we introduce the energy cost per amino acid (ECPA) to quantitatively characterize the use of 20 amino acids during protein synthesis in human cells. By analyzing gene expression data from The Cancer Genome Atlas, we find that cancer cells evolve to utilize amino acids more economically by optimizing gene expression profile and ECPA shows robust prognostic power across many cancer types. We further validate this pattern in an experimental evolution of xenograft tumors. Our ECPA analysis reveals a common principle during cancer evolution.
Modulation of proteoglycan receptor PTPσ enhances MMP-2 activity to promote recovery from multiple sclerosis
Authors: Luo Fucheng , Tran Amanda Phuong , Xin Li , Sanapala Chandrika , Lang Bradley T. , Silver Jerry , Yang Yan 
Published: October 2018

AbstractMultiple Sclerosis (MS) is characterized by focal CNS inflammation leading to the death of oligodendrocytes (OLs) with subsequent demyelination, neuronal degeneration, and severe functional deficits. Inhibitory chondroitin sulfate proteoglycans (CSPGs) are increased in the extracellular matrix in the vicinity of MS lesions and are thought to play a critical role in myelin regeneration failure. We here show that CSPGs curtail remyelination through binding with their cognate receptor, protein tyrosine phosphatase σ (PTPσ) on oligodendrocyte progenitor cells (OPCs). We report that inhibition of CSPG/PTPσ signaling by systemically deliverable Intracellular Sigma Peptide (ISP), promotes OPC migration, maturation, remyelination, and functional recovery in animal models of MS. Furthermore, we report a downstream molecular target of PTPσ modulation in OPCs involving upregulation of the protease MMP-2 that allows OPCs to enzymatically digest their way through CSPGs. In total, we demonstrate a critical role of PTPσ/CSPG interactions in OPC remyelination in MS.
High-efficiency optogenetic silencing with soma-targeted anion-conducting channelrhodopsins
Authors: Mahn Mathias , Gibor Lihi , Patil Pritish , Cohen-Kashi Malina Katayun , Oring Shir , Printz Yoav , Levy Rivka , Lampl Ilan , Yizhar Ofer 
Published: October 2018

AbstractOptogenetic silencing allows time-resolved functional interrogation of defined neuronal populations. However, the limitations of inhibitory optogenetic tools impose stringent constraints on experimental paradigms. The high light power requirement of light-driven ion pumps and their effects on intracellular ion homeostasis pose unique challenges, particularly in experiments that demand inhibition of a widespread neuronal population in vivo. Guillardia theta anion-conducting channelrhodopsins (GtACRs) are promising in this regard, due to their high single-channel conductance and favorable photon-ion stoichiometry. However, GtACRs show poor membrane targeting in mammalian cells, and the activity of such channels can cause transient excitation in the axon due to an excitatory chloride reversal potential in this compartment. Here, we address these problems by enhancing membrane targeting and subcellular compartmentalization of GtACRs. The resulting soma-targeted GtACRs show improved photocurrents, reduced axonal excitation and high light sensitivity, allowing highly efficient inhibition of neuronal activity in the mammalian brain.
Quasiparticle interference and nonsymmorphic effect on a floating band surface state of ZrSiSe
Authors: Zhu Zhen , Chang Tay-Rong , Huang Cheng-Yi , Pan Haiyang , Nie Xiao-Ang , Wang Xin-Zhe , Jin Zhe-Ting , Xu Su-Yang , Huang Shin-Ming , Guan Dan-Dan , Wang Shiyong , Li Yao-Yi , Liu Canhua , Qian Dong , Ku Wei , Song Fengqi , Lin Hsin , Zheng Hao , Jia Jin-Feng 
Published: October 2018

AbstractNon-symmorphic crystals are generating great interest as they are commonly found in quantum materials, like iron-based superconductors, heavy-fermion compounds, and topological semimetals. A new type of surface state, a floating band, was recently discovered in the nodal-line semimetal ZrSiSe, but also exists in many non-symmorphic crystals. Little is known about its physical properties. Here, we employ scanning tunneling microscopy to measure the quasiparticle interference of the floating band state on ZrSiSe (001) surface and discover rotational symmetry breaking interference, healing effect and half-missing-type anomalous Umklapp scattering. Using simulation and theoretical analysis we establish that the phenomena are characteristic properties of a floating band surface state. Moreover, we uncover that the half-missing Umklapp process is derived from the glide mirror symmetry, thus identify a non-symmorphic effect on quasiparticle interferences. Our results may pave a way towards potential new applications of nanoelectronics.
Genome-wide association studies of brain imaging phenotypes in UK Biobank
Authors: Elliott Lloyd T. , Sharp Kevin , Alfaro-Almagro Fidel , Shi Sinan , Miller Karla L. , Douaud Gwenaëlle , Marchini Jonathan , Smith Stephen M. 
Published: October 2018

AbstractThe genetic architecture of brain structure and function is largely unknown. To investigate this, we carried out genome-wide association studies of 3,144 functional and structural brain imaging phenotypes from UK Biobank (discovery dataset 8,428 subjects). Here we show that many of these phenotypes are heritable. We identify 148 clusters of associations between single nucleotide polymorphisms and imaging phenotypes that replicate at P < 0.05, when we would expect 21 to replicate by chance. Notable significant, interpretable associations include: iron transport and storage genes, related to magnetic susceptibility of subcortical brain tissue; extracellular matrix and epidermal growth factor genes, associated with white matter micro-structure and lesions; genes that regulate mid-line axon development, associated with organization of the pontine crossing tract; and overall 17 genes involved in development, pathway signalling and plasticity. Our results provide insights into the genetic architecture of the brain that are relevant to neurological and psychiatric disorders, brain development and ageing.
The UK Biobank resource with deep phenotyping and genomic data
Authors: Bycroft Clare , Freeman Colin , Petkova Desislava , Band Gavin , Elliott Lloyd T. , Sharp Kevin , Motyer Allan , Vukcevic Damjan , Delaneau Olivier , O’Connell Jared , Cortes Adrian , Welsh Samantha , Young Alan , Effingham Mark , McVean Gil , Leslie Stephen , Allen Naomi , Donnelly Peter , Marchini Jonathan 
Published: October 2018

AbstractThe UK Biobank project is a prospective cohort study with deep genetic and phenotypic data collected on approximately 500,000 individuals from across the United Kingdom, aged between 40 and 69 at recruitment. The open resource is unique in its size and scope. A rich variety of phenotypic and health-related information is available on each participant, including biological measurements, lifestyle indicators, biomarkers in blood and urine, and imaging of the body and brain. Follow-up information is provided by linking health and medical records. Genome-wide genotype data have been collected on all participants, providing many opportunities for the discovery of new genetic associations and the genetic bases of complex traits. Here we describe the centralized analysis of the genetic data, including genotype quality, properties of population structure and relatedness of the genetic data, and efficient phasing and genotype imputation that increases the number of testable variants to around 96 million. Classical allelic variation at 11 human leukocyte antigen genes was imputed, resulting in the recovery of signals with known associations between human leukocyte antigen alleles and many diseases.
Mannich base limits Candida albicans virulence by inactivating Ras-cAMP-PKA pathway
Authors: Rajasekharan Satish Kumar , Kamalanathan Chakkaravarthi , Ravichandran Vinothkannan , Ray Arvind Kumar , Satish Ann Susan , Mohanvel Sucharitha Kannappan 
Published: October 2018

AbstractMannich bases and its derivatives are regarded as supreme pharmacophores in therapeutics. The study investigates the antimycotic potential of Mannich bases, 1-((1H-benzimidazol-1-yl) methyl) urea (C1) and 1-((3-hydroxynapthalen-2-yl) methyl) thiourea (C2), against Candida albicans. Biofilm and hyphal inhibitory activities of the Mannich bases were tested by crystal violet quantification, fluorescence imaging cAMP rescue, qRT PCR, and by molecular docking analysis. The compounds inhibited the biofilms of C. albicans and restrained the filamentation abilities of the pathogen. Structure-activity relationship studies revealed that the presence of urea or thiourea moiety in the tail section is essential for interacting with adenylate cyclase (AC). The Mannich bases seemed to block Ras-cAMP-PKA pathway by inhibiting second messenger activity required for hyphal induction and biofilm formation. In conclusion, the study warrants point-of-care testing of C1/C2 and provides a starting point for deriving several structurally modified Mannich bases which might plausibly replace the prevailing antimycotic drugs in future.
Metabolic abnormalities in adult T-cell leukemia/lymphoma and induction of specific leukemic cell death using photodynamic therapy
Authors: Oka Takashi , Mizuno Hajime , Sakata Masumi , Fujita Hirofumi , Yoshino Tadashi , Yamano Yoshihisa , Utsumi Kozo , Masujima Tsutomu , Utsunomiya Atae 
Published: October 2018

AbstractAdult T-cell leukemia/lymphoma (ATL) is an aggressive T-cell neoplasm caused by human T-cell leukemia virus type I (HTLV-I). Therapeutic interventions have not been associated with satisfactory outcomes. We showed that the porphyrin metabolic pathway preferentially accumulates the endogenous photosensitive metabolite, protoporphyrin IX (PpIX) in ATL, after a short-term culture with 5-aminolevulinic acid (ALA). PpIX accumulated 10–100-fold more in ATL leukemic cells when compared to healthy peripheral blood mononuclear cells (PBMCs). Patient specimens showed dynamic changes in flow cytometry profiles during the onset and progression of ATL. Furthermore, 98.7% of ATL leukemic cell death in the ATL patient specimens could be induced with 10 min of visible light exposure, while 77.5% of normal PBMCs survived. Metabolomics analyses revealed that a specific stage of the metabolic pathway progressively deteriorated with HTLV-I infection and at the onset of ATL. Therefore, this method will be useful in diagnosing and identifying high-risk HTLV-I carriers with single cell resolutions. Photodynamic therapy in the circulatory system may be a potential treatment due to its highly-specific, non-invasive, safe, simultaneous, and repeatedly-treatable modalities.
Plantar cutaneous afferents influence the perception of Subjective Visual Vertical in quiet stance
Authors: Foisy A. , Kapoula Z. 
Published: October 2018

AbstractThe estimation of Subjective Visual Vertical (SVV) involves the allocentric, gravitational and egocentric references, which are built by visual, vestibular and somatosensory afferents. Our goals were to assess the influence of plantar cutaneous afferents on the perception of SVV, and to see if there is a difference according to the efficiency of plantar cutaneous afferents. We recruited 48 young and healthy subjects and assessed their SVV and postural performances in quiet stance with a force platform, at 40 or 200 cm, in four ground conditions: on firm ground, on foam, with a bilateral, or with a unilateral 3 mm arch support. We also assessed the efficiency of our subjects’ plantar afferents with the plantar quotient method and divided them in two groups: subjects with a normal use of plantar afferents and subjects with Plantar Exteroceptive Inefficiency (PEI). The results showed significant decreases in the counter clockwise SVV deviation only with the unilateral arch support, at near distance, and among the typically behaving subjects. We conclude that asymmetric foot cutaneous afferents are able to bias the egocentric vertical reference and hence influence the perception of SVV. This influence disappears among subjects with PEI, probably because of a distortion of the plantar signal.
Aberrant neuronal differentiation is common in glioma but is associated neither with epileptic seizures nor with better survival
Authors: Beier Christoph Patrick , Rasmussen Tine , Dahlrot Rikke Hedegaard , Tenstad Helene Broch , Aarø Julie Slinning , Sørensen Mai Froberg , Heimisdóttir Sólborg Berglind , Sørensen Mia Dahl , Svenningsen Per , Riemenschneider Markus J. , Beier Dagmar , Kristensen Bjarne Winther 
Published: October 2018

AbstractThe mechanisms of glioma-associated seizures (GAS) have yet to be fully elucidated. Proneural subtype, isocitrate dehydrogenase 1 (IDH1) mutations, and epileptic seizures are closely associated suggesting that aberrant neuronal differentiation contributes to glioma-associated seizures. In a population-based cohort (n = 236), lack of stem cell marker expression (nestin, musashi) was significantly associated with IDH1 mutations and GAS at diagnosis. In vitro data suggested an association of IDH1 mutations and a more differentiated phenotype. Out of eight glioma stem cell (GSC) lines, seven revealed positivity for the synaptic marker protein synaptophysin. Three had synapse-like structures identified by electron microscopy and were either vGlut1 (glutamatergic) or GAD67 (GABAergic) positive. In vivo, >10% synaptophysin-positive tumour cells were present in >90% of all gliomas. Synaptophysin expression was associated with proneural subtype and vGlut1 expression, suggesting that most synapse-like structures in glioma are glutamatergic. However, we found null associations between vGlut1 protein/mRNA expression and survival, GAS at onset, development of GAS after resection, and refractory GAS. Synapse-like structures were neither functional nor activated by spontaneous action potentials or cellular networks. Thus, aberrant neuronal differentiation including glutamatergic synapse-like structures is detectable in glioma but is associated neither with epileptic seizures nor with better survival.
Identification of a Novel OX40L+ Dendritic Cell Subset That Selectively Expands Regulatory T cells
Authors: Marinelarena Alejandra , Bhattacharya Palash , Kumar Prabhakaran , Maker Ajay V. , Prabhakar Bellur S. 
Published: October 2018

AbstractWe have previously shown GM-CSF derived bone-marrow dendritic cells (G-BMDCs) can induce the selective expansion of Tregs through the surface-bound molecule OX40L; however, the physiological role of this ex vivo derived DC subset remained to be elucidated. We determined GM-CSF administration to mice induced the generation of in vivo derived OX40L+ DCs, phenotypically similar to ex vivo OX40L+G-BMDCs, in the spleen, brachial lymph nodes and liver. The generation of OX40L+ DCs correlated with increased percentages of functionally suppressive Tregs in the spleen, brachial lymph nodes, and liver of GM-CSF treated mice. DCs from GM-CSF treated mice expanded Tregs in CD4+ T-cell co-cultures in an OX40L dependent manner, suggesting OX40L+ DCs may play a role in peripheral Treg homeostasis. Furthermore, comparing the transcriptome data of OX40L+ DCs to that of all immune cell types revealed OX40L+ DCs to be distinct from steady-state immune cells and, microarray analysis of OX40L+G-BMDCs and OX40L−G-BMDCs revealed higher expression of molecules that are associated with tolerogenic phenotype and could play important roles in the function of OX40L+ DCs. These findings suggest that OX40L+ DCs may represent a unique DC subset induced under inflammatory conditions that may play an essential role in maintaining Treg homeostasis.
Rapid and selective concentration of bacteria, viruses, and proteins using alternating current signal superimposition on two coplanar electrodes
Authors: Han Chang-Ho , Woo Seong Yong , Bhardwaj Jyoti , Sharma Abhinav , Jang Jaesung 
Published: October 2018

AbstractDielectrophoresis (DEP) is usually effective close to the electrode surface. Several techniques have been developed to overcome its drawbacks and to enhance dielectrophoretic particle capture. Here we present a simple technique of superimposing alternating current DEP (high-frequency signals) and electroosmosis (EO; low-frequency signals) between two coplanar electrodes (gap: 25 μm) using a lab-made voltage adder for rapid and selective concentration of bacteria, viruses, and proteins, where we controlled the voltages and frequencies of DEP and EO separately. This signal superimposition technique enhanced bacterial capture (Escherichia coli K-12 against 1-μm-diameter polystyrene beads) more selectively (>99%) and rapidly (~30 s) at lower DEP (5 Vpp) and EO (1.2 Vpp) potentials than those used in the conventional DEP capture studies. Nanometer-sized MS2 viruses and troponin I antibody proteins were also concentrated using the superimposed signals, and significantly more MS2 and cTnI-Ab were captured using the superimposed signals than the DEP (10 Vpp) or EO (2 Vpp) signals alone (p < 0.035) between the two coplanar electrodes and at a short exposure time (1 min). This technique has several advantages, such as simplicity and low cost of electrode fabrication, rapid and large collection without electrolysis.
Functionalization of gold-nanoparticles by the Clostridium perfringens enterotoxin C-terminus for tumor cell ablation using the gold nanoparticle-mediated laser perforation technique
Authors: Becker Annegret , Leskau Miriam , Schlingmann-Molina Barbara L. , Hohmeier Susanne C. , Alnajjar Suhayla , Murua Escobar Hugo , Ngezahayo Anaclet 
Published: October 2018

AbstractA recombinant produced C-terminus of the C. perfringens enterotoxin (C-CPE) was conjugated to gold nanoparticles (AuNPs) to produce a C-CPE-AuNP complex (C-CPE-AuNP). By binding to claudins, the C- CPE should allow to target the AuNPs onto the claudin expressing tumor cells for a subsequent cell killing by application of the gold nanoparticle-mediated laser perforation (GNOME-LP) technique. Using qPCR and immunocytochemistry, we identified the human Caco-2, MCF-7 and OE-33 as well as the canine TiHoDMglCarc1305 as tumor cells expressing claudin-3, -4 and -7. Transepithelial electrical resistance (TEER) measurements of Caco-2 cell monolayer showed that the recombinant C-CPE bound to the claudins. GNOME-LP at a laser fluence of 60 mJ/cm2 and a scanning speed of 0.5 cm/s specifically eliminated more than 75% of claudin expressing human and canine cells treated with C-CPE-AuNP. The same laser fluence did not affect the cells when non-functionalized AuNPs were used. Furthermore, most of the claudin non-expressing cells treated with C-CPE-AuNP were not killed by GNOME-LP. Additionally, application of C-CPE-AuNP to spheroids formed by MCF-7 and OE-33 cells grown in Matrigel reduced spheroid area. The results demonstrate that specific ablation of claudin expressing tumor cells is efficiently increased by activated C-CPE functionalized AuNPs using optical methods.
Accuracy of theoretical catalysis from a model of iron-catalyzed ammonia synthesis
Authors: Kepp Kasper P. 
Published: October 2018

AbstractDensity functional theory is central to the study of catalytic processes, but its accuracy is widely debated, and lack of data complicates accuracy estimates. To address these issues, this work explores a simple eight-step process of iron-catalyzed ammonia synthesis. The models’s importance lies in the availability of experimental data and the accessibility of coupled-cluster CCSD(T) calculations, enabling direct assessment of method accuracy for all reaction steps. While many functionals accurately describe the net process N2 + 3H2 → NH3, errors of +100 kJ mol−1 occur in many individual steps for popular functionals such as PBE, RPBE, and B3LYP, which are much worse than commonly assumed. Inclusion of the stoichiometric reaction coefficients reveals major accuracy bottlenecks surprisingly distinct from the N–N dissociation step and dependent on the applied functional. More focus should be directed to these problematic steps in order to improve the accuracy of modeling the catalytic process.