bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression-based drug screening of neural progenitor cells from individuals with schizophrenia
Authors: Readhead Benjamin , Hartley Brigham J. , Eastwood Brian J. , Collier David A. , Evans David , Farias Richard , He Ching , Hoffman Gabriel , Sklar Pamela , Dudley Joel T. , Schadt Eric E. , Savić Radoslav , Brennand Kristen J. 
Published: October 2018

AbstractA lack of biologically relevant screening models hinders the discovery of better treatments for schizophrenia (SZ) and other neuropsychiatric disorders. Here we compare the transcriptional responses of 8 commonly used cancer cell lines (CCLs) directly with that of human induced pluripotent stem cell (hiPSC)-derived neural progenitor cells (NPCs) from 12 individuals with SZ and 12 controls across 135 drugs, generating 4320 unique drug-response transcriptional signatures. We identify those drugs that reverse post-mortem SZ-associated transcriptomic signatures, several of which also differentially regulate neuropsychiatric disease-associated genes in a cell type (hiPSC NPC vs. CCL) and/or a diagnosis (SZ vs. control)-dependent manner. Overall, we describe a proof-of-concept application of transcriptomic drug screening to hiPSC-based models, demonstrating that the drug-induced gene expression differences observed with patient-derived hiPSC NPCs are enriched for SZ biology, thereby revealing a major advantage of incorporating cell type and patient-specific platforms in drug discovery.
The signalling conformation of the insulin receptor ectodomain
Authors: Weis Felix , Menting John G. , Margetts Mai B. , Chan Shu Jin , Xu Yibin , Tennagels Norbert , Wohlfart Paulus , Langer Thomas , Müller Christoph W. , Dreyer Matthias K. , Lawrence Michael C. 
Published: October 2018

AbstractUnderstanding the structural biology of the insulin receptor and how it signals is of key importance in the development of insulin analogs to treat diabetes. We report here a cryo-electron microscopy structure of a single insulin bound to a physiologically relevant, high-affinity version of the receptor ectodomain, the latter generated through attachment of C-terminal leucine zipper elements to overcome the conformational flexibility associated with ectodomain truncation. The resolution of the cryo-electron microscopy maps is 3.2 Å in the insulin-binding region and 4.2 Å in the membrane-proximal region. The structure reveals how the membrane proximal domains of the receptor come together to effect signalling and how insulin’s negative cooperativity of binding likely arises. Our structure further provides insight into the high affinity of certain super-mitogenic insulins. Together, these findings provide a new platform for insulin analog investigation and design.
Sleep-like cortical OFF-periods disrupt causality and complexity in the brain of unresponsive wakefulness syndrome patients
Authors: Rosanova M. , Fecchio M. , Casarotto S. , Sarasso S. , Casali A. G. , Pigorini A. , Comanducci A. , Seregni F. , Devalle G. , Citerio G. , Bodart O. , Boly M. , Gosseries O. , Laureys S. , Massimini M. 
Published: October 2018

AbstractUnresponsive wakefulness syndrome (UWS) patients may retain intact portions of the thalamocortical system that are spontaneously active and reactive to sensory stimuli but fail to engage in complex causal interactions, resulting in loss of consciousness. Here, we show that loss of brain complexity after severe injuries is due to a pathological tendency of cortical circuits to fall into silence (OFF-period) upon receiving an input, a behavior typically observed during sleep. Spectral and phase domain analysis of EEG responses to transcranial magnetic stimulation reveals the occurrence of OFF-periods in the cortex of UWS patients (N = 16); these events never occur in healthy awake individuals (N = 20) but are similar to those detected in healthy sleeping subjects (N = 8). Crucially, OFF-periods impair local causal interactions, and prevent the build-up of global complexity in UWS. Our findings link potentially reversible local events to global brain dynamics that are relevant for pathological loss and recovery of consciousness.
Design and self-assembly of hexahedral coordination cages for cascade reactions
Authors: Jiao Jingjing , Li Zijian , Qiao Zhiwei , Li Xu , Liu Yan , Dong Jinqiao , Jiang Jianwen , Cui Yong 
Published: October 2018

AbstractThe search for supramolecular reactors that contain no catalytically active sites but can promote chemical transformations has received significant attention, but it remains a synthetic challenge. Here we demonstrate a strategy of incorporating bulky and electro-rich aromatic linkers into metallocages to induce cascade reactions. Two hexahedral cages with a framework formula [(Zn8L6)(OTf)16] are assembled from six tetrakis-bidentate ligands derived from tetraphenylethylene and eight zinc(II)tris(pyridylimine) centers. The cage cavities can accommodate different molecules such as anthranilamide and aromatic aldehyde through supramolecular interactions, allowing for a cascade condensation and cyclization to produce nonplanar 2,3-dihyroquinazolinones. The reaction is highly efficient with high rate enhancements (up to kcat/kuncat = 38,000) and multiple turnovers compared to the bulk reaction mixture. Control experiments and molecular simulations suggest that the acceleration is attributed to inherent strength of binding affinity for reactants and the release of products to establish catalytic turnover is due to the host−guest geometry discrepancy.
Ballistic tracks in graphene nanoribbons
Authors: Aprojanz Johannes , Power Stephen R. , Bampoulis Pantelis , Roche Stephan , Jauho Antti-Pekka , Zandvliet Harold J. W. , Zakharov Alexei A. , Tegenkamp Christoph 
Published: October 2018

AbstractHigh quality graphene nanoribbons epitaxially grown on the sidewalls of silicon carbide (SiC) mesa structures stand as key building blocks for graphene-based nanoelectronics. Such ribbons display 1D single-channel ballistic transport at room temperature with exceptionally long mean free paths. Here, using spatially-resolved two-point probe (2PP) measurements, we selectively access and directly image a range of individual transport modes in sidewall ribbons. The signature of the independently contacted channels is a sequence of quantised conductance plateaus for different probe positions. These result from an interplay between edge magnetism and asymmetric terminations at opposite ribbon edges due to the underlying SiC structure morphology. Our findings demonstrate a precise control of transport through multiple, independent, ballistic tracks in graphene-based devices, opening intriguing pathways for quantum information device concepts.
Prospective observational cohort study of symptom control prediction in paediatric asthma by using the Royal College of Physicians three questions
Authors: Andrews Glen , Lo David K. H. , Richardson Matthew , Wilson Andrew , Gaillard Erol A. 
Published: October 2018

AbstractThe Royal College of Physicians three questions (RCP3Q) is widely used for assessing asthma control within primary care in the UK, despite limited evidence in children. This study compared the RCP3Q as a tool for assessing asthma control in children (5–16 years) against the validated Asthma Control Test (ACT), Childhood Asthma Control Test (C-ACT), and Mini-Paediatric Quality of Life Questionnaire (MiniPAQLQ). We conducted a prospective observational cohort study involving children from eight primary care practices in Leicestershire. Children with doctor diagnosed asthma, or receiving regular asthma medication, were invited to participate. A total of 319 participants completed the MiniPAQLQ and the C-ACT/ACT questionnaires, before RCP3Q responses were collected as part of their routine asthma review conducted immediately afterwards. RCP3Q sensitivity for detecting uncontrolled asthma ranged from 43–60% and specificity from 80–82%. Using an RCP3Q score ≥2 to predict uncontrolled asthma and an RCP3Q score of zero to predict well-controlled asthma resulted in 10% of participants misclassified as uncontrolled and 8% as well-controlled, respectively. Using an RCP3Q threshold score of ≥1 resulted in 25% of participants being misclassified as uncontrolled. Our data suggests limited utility of the RCP3Q to assess asthma control in children. Alternative indicators of asthma control, such as the validated Asthma Control Test and the Children’s Asthma Control Test should be considered instead.
Interspecies cross-feeding orchestrates carbon degradation in the rumen ecosystem
Authors: Solden Lindsey M. , Naas Adrian E. , Roux Simon , Daly Rebecca A. , Collins William B. , Nicora Carrie D. , Purvine Sam O. , Hoyt David W. , Schückel Julia , Jørgensen Bodil , Willats William , Spalinger Donald E. , Firkins Jeffrey L. , Lipton Mary S. , Sullivan Matthew B. , Pope Phillip B. , Wrighton Kelly C. 
Published: October 2018

AbstractBecause of their agricultural value, there is a great body of research dedicated to understanding the microorganisms responsible for rumen carbon degradation. However, we lack a holistic view of the microbial food web responsible for carbon processing in this ecosystem. Here, we sampled rumen-fistulated moose, allowing access to rumen microbial communities actively degrading woody plant biomass in real time. We resolved 1,193 viral contigs and 77 unique, near-complete microbial metagenome-assembled genomes, many of which lacked previous metabolic insights. Plant-derived metabolites were measured with NMR and carbohydrate microarrays to quantify the carbon nutrient landscape. Network analyses directly linked measured metabolites to expressed proteins from these unique metagenome-assembled genomes, revealing a genome-resolved three-tiered carbohydrate-fuelled trophic system. This provided a glimpse into microbial specialization into functional guilds defined by specific metabolites. To validate our proteomic inferences, the catalytic activity of a polysaccharide utilization locus from a highly connected metabolic hub genome was confirmed using heterologous gene expression. Viral detected proteins and linkages to microbial hosts demonstrated that phage are active controllers of rumen ecosystem function. Our findings elucidate the microbial and viral members, as well as their metabolic interdependencies, that support in situ carbon degradation in the rumen ecosystem.
Two alternatively-spliced human nebulin isoforms with either exon 143 or exon 144 and their developmental regulation
Authors: Lam Le Thanh , Holt Ian , Laitila Jenni , Hanif Mubashir , Pelin Katarina , Wallgren-Pettersson Carina , Sewry Caroline A. , Morris Glenn E. 
Published: October 2018

AbstractNebulin is a very large protein required for assembly of the contractile machinery in muscle. Mutations in the nebulin gene NEB are a common cause of nemaline myopathy. Nebulin mRNA is alternatively-spliced so that each mRNA contains either exon 143 or exon 144. We have produced monoclonal antibodies specific for the regions of nebulin encoded by these two exons, enabling analysis of expression of isoforms at the protein level for the first time. All antibodies recognized a protein of the expected size (600–900 kD) and stained cross-striations of sarcomeres in muscle sections. Expression of exon 143 is developmentally-regulated since newly-formed myotubes in cell culture expressed nebulin with exon 144 only; this was confirmed at the mRNA level by qPCR. In fetal muscle, nebulin with exon 143 was expressed in some myotubes by 12-weeks of gestation and strongly-expressed in most myotubes by 17-weeks. In mature human muscle, the exon 144 antibody stained all fibres, but the exon 143 antibody staining varied from very strong in some fibres to almost-undetectable in other fibres. The results show that nebulin containing exon 144 is the default isoform early in myogenesis, while regulated expression of nebulin containing exon 143 occurs at later stages of muscle development.
Acoustophoretic Orientation of Red Blood Cells for Diagnosis of Red Cell Health and Pathology
Authors: Rico Laura G. , Juncà Jordi , Ward Mike D. , Bradford Jolene A. , Bardina Jorge , Petriz Jordi 
Published: October 2018

AbstractDistortions of the normal bi-concave disc shape for red blood cells (RBCs) appear in a number of pathologies resulting from defects in cell membrane skeletal architecture, erythrocyte ageing, and mechanical damage. We present here the potential of acoustic cytometry for developing new approaches to light-scattering based evaluation of red blood cell disorders and of the effects of storage and ageing on changes or damage to RBCs membranes. These approaches could be used to immediately evaluate the quality of erythrocytes prior to blood donation and following transfusion. They could also be applied to studying RBC health in diseases and other pathologies, such as artificial heart valve hemolysis, thermal damage or osmotic fragility. Abnormal distributions of erythrocytes can typically be detected after just 30 to 45 seconds of acquisition time using 1–2 µL starting blood volumes.
The first set of universal nuclear protein-coding loci markers for avian phylogenetic and population genetic studies
Authors: Liu Yang , Liu Simin , Yeh Chia-Fen , Zhang Nan , Chen Guoling , Que Pinjia , Dong Lu , Li Shou-hsien 
Published: October 2018

AbstractMultiple nuclear markers provide genetic polymorphism data for molecular systematics and population genetic studies. They are especially required for the coalescent-based analyses that can be used to accurately estimate species trees and infer population demographic histories. However, in avian evolutionary studies, these powerful coalescent-based methods are hindered by the lack of a sufficient number of markers. In this study, we designed PCR primers to amplify 136 nuclear protein-coding loci (NPCLs) by scanning the published Red Junglefowl (Gallus gallus) and Zebra Finch (Taeniopygia guttata) genomes. To test their utility, we amplified these loci in 41 bird species representing 23 Aves orders. The sixty-three best-performing NPCLs, based on high PCR success rates, were selected which had various mutation rates and were evenly distributed across 17 avian autosomal chromosomes and the Z chromosome. To test phylogenetic resolving power of these markers, we conducted a Neoavian phylogenies analysis using 63 concatenated NPCL markers derived from 48 whole genomes of birds. The resulting phylogenetic topology, to a large extent, is congruence with results resolved by previous whole genome data. To test the level of intraspecific polymorphism in these makers, we examined the genetic diversity in four populations of the Kentish Plover (Charadrius alexandrinus) at 17 of NPCL markers chosen at random. Our results showed that these NPCL markers exhibited a level of polymorphism comparable with mitochondrial loci. Therefore, this set of pan-avian nuclear protein-coding loci has great potential to facilitate studies in avian phylogenetics and population genetics.
SMTracker: a tool for quantitative analysis, exploration and visualization of single-molecule tracking data reveals highly dynamic binding of B. subtilis global repressor AbrB throughout the genome
Authors: Rösch Thomas C. , Oviedo-Bocanegra Luis M. , Fritz Georg , Graumann Peter L. 
Published: October 2018

AbstractSingle-particle (molecule) tracking (SPT/SMT) is a powerful method to study dynamic processes in living cells at high spatial and temporal resolution. Even though SMT is becoming a widely used method in bacterial cell biology, there is no program employing different analytical tools for the quantitative evaluation of tracking data. We developed SMTracker, a MATLAB-based graphical user interface (GUI) for automatically quantifying, visualizing and managing SMT data via five interactive panels, allowing the user to interactively explore tracking data from several conditions, movies and cells on a track-by-track basis. Diffusion constants are calculated a) by a Gaussian mixture model (GMM) panel, analyzing the distribution of positional displacements in x- and y-direction using a multi-state diffusion model (e.g. DNA-bound vs. freely diffusing molecules), and inferring the diffusion constants and relative fraction of molecules in each state, or b) by square displacement analysis (SQD), using the cumulative probability distribution of square displacements to estimate the diffusion constants and relative fractions of up to three diffusive states, or c) through mean-squared displacement (MSD) analyses, allowing the discrimination between Brownian, sub- or superdiffusive behavior. A spatial distribution analysis (SDA) panel analyzes the subcellular localization of molecules, summarizing the localization of trajectories in 2D- heat maps. Using SMTracker, we show that the global transcriptional repressor AbrB performs highly dynamic binding throughout the Bacillus subtilis genome, with short dwell times that indicate high on/off rates in vivo. While about a third of AbrB molecules are in a DNA-bound state, 40% diffuse through the chromosome, and the remaining molecules freely diffuse through the cells. AbrB also forms one or two regions of high intensity binding on the nucleoids, similar to the global gene silencer H-NS in Escherichia coli, indicating that AbrB may also confer a structural function in genome organization.
Metabolic fingerprints of Serratia liquefaciens under simulated Martian conditions using Biolog GN2 microarrays
Authors: Schwendner Petra , Schuerger Andrew C. 
Published: October 2018

AbstractMicroorganisms growing at atmospheric pressures of 0.7 kPa may have a significant impact on the search for life on Mars. Data on their nutrient requirements in a simulated Martian environment are required to ascertain both the potential risk of forward contamination and the potential of past or present habitability of Mars. Serratia liquefaciens can grow at concomitant conditions of low pressure, low temperature, and anoxic atmosphere. Changes in the metabolic fingerprint of S. liquefaciens grown under varying physical conditions including diverse atmospheric pressures (0.7 kPa to 101.3 kPa), temperatures (30 °C or 0 °C), and atmospheric gas compositions (Earth or CO2) were investigated using Biolog GN2 assays. Distinct patterns for each condition were observed. Above 10 kPa S. liquefaciens performed similar to Earth-normal pressure conditions (101.3 kPa) whereas below 10 kPa shifts in metabolic patterns were observed. The differences indicated a physiological alteration in which S. liquefaciens lost its ability to metabolize the majority of the provided carbon sources at 0.7 kPa with a significant decrease in the oxidation of amino acids. By measuring the physiological responses to different carbon sources we were able to identify nutritional constraints that support cellular replication under simulated shallow Mars subsurface conditions.
Evaluation of the cardioprotective potential of extracellular vesicles – a systematic review and meta-analysis
Authors: Wendt Sebastian , Goetzenich Andreas , Goettsch Claudia , Stoppe Christian , Bleilevens Christian , Kraemer Sandra , Benstoem Carina 
Published: October 2018

AbstractCardiovascular diseases are the main cause of death worldwide, demanding new treatments and interventions. Recently, extracellular vesicles (EVs) came in focus as important carriers of protective molecules such as miRNAs and proteins which might contribute to e.g. improved cardiac function after myocardial infarction. EVs can be secreted from almost every cell type in the human body and can be transferred via the bloodstream in almost every compartment. To provide an all-encompassing overview of studies investigating these beneficial properties of EVs we performed a systematic review/meta-analysis of studies investigating the cardioprotective characteristics of EVs. Forty-three studies were investigated and catalogued according to the EV source. We provide an in-depth analysis of the purification method, size of the EVs, the conducted experiments to investigate the beneficial properties of EVs as well as the major effector molecule encapsulated in EVs mediating protection. This study provides evidence that EVs from different cell types and body fluids provide cardioprotection in different in vivo and in vitro studies. A meta-analysis was performed to estimate the underlying effect size. In conclusion, we demonstrated that EVs from different sources might serve as a promising tool for treating cardiovascular diseases in the future.
Establishment of a dual-wavelength spectrophotometric method for analysing and detecting carbapenemase-producing Enterobacteriaceae
Authors: Takeuchi Dan , Akeda Yukihiro , Sugawara Yo , Sakamoto Noriko , Yamamoto Norihisa , Shanmugakani Rathina Kumar , Ishihara Takuma , Shintani Ayumi , Tomono Kazunori , Hamada Shigeyuki 
Published: October 2018

AbstractThe spread of carbapenemase-producing Enterobacteriaceae (CPE) is an increasing global public health concern. The development of simple and reliable methods for CPE detection is required in the clinical setting. This study aimed to establish a dual-wavelength measurement method using an ultraviolet–visible spectrophotometer to rapidly quantify imipenem hydrolysis in bacterial cell suspensions. The hydrolytic activities of 148 strains including various CPE strains (Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, and Enterobacter aerogenes containing the blaIMP, blaKPC, blaNDM, blaOXA, and blaVIM genes) were measured and analysed. A cut-off value was obtained for differentiation between CPE and non-CPE strains, and the method had high sensitivity (100%) and specificity (100%) within 60 min. Our system has potential clinical applications in detecting CPE.
Synthesis, characterization and in vitro biological evaluation of two matrine derivatives
Authors: Cheng Xingan , Ye Jingmin , He Huiqing , Liu Zhanmei , Xu Chunbao , Wu Bo , Xiong Xialing , Shu Xugang , Jiang Xuhong , Qin Xiangjing 
Published: October 2018

AbstractMatrine is a traditional Chinese medicine and botanical pesticide with broad biological activities, including pharmacological and agricultural activities. In present work, two matrine derivatives have been successfully synthesized via introducing indole and cyclohexylamino to 13 position of matrine, respectively, with sophocarpine as starting material, and structurally characterized via infrared spectroscopy(IR), MS, 1 H NMR, 13 C NMR and X-ray crystal diffraction. The results of the in vitro biological activity tests showed that these two matrine derivatives exhibited even better activities against human cancer cells Hela229 and insect cell line Sf9 from Spodoptera frugiperda (J. E. Smith) than that of parent matrine, suggesting that the heterocyclic or cyclic group can dramatically increase the biological activity of matrine. It is worth to mention that 13-indole-matrine could possibly inhibit the growth of insect cells or human cancer cells by inducing cell apoptosis. The results of the present study provide useful information for further structural modifications of these compounds and for exploring new, potent anti-cancer agents and environment friendly pesticides.