bluuebunny/crossref_metadata_2025_split huggingface dataset:
Workflow optimization of whole genome amplification and targeted panel sequencing for CTC mutation detection
Authors: Liu Haiyan E. , Triboulet Melanie , Zia Amin , Vuppalapaty Meghah , Kidess-Sigal Evelyn , Coller John , Natu Vanita S. , Shokoohi Vida , Che James , Renier Corinne , Chan Natalie H. , Hanft Violet R. , Jeffrey Stefanie S. , Sollier-Christen Elodie 
Published: October 2017

AbstractGenomic characterization of circulating tumor cells (CTCs) may prove useful as a surrogate for conventional tissue biopsies. This is particularly important as studies have shown different mutational profiles between CTCs and ctDNA in some tumor subtypes. However, isolating rare CTCs from whole blood has significant hurdles. Very limited DNA quantities often can’t meet NGS requirements without whole genome amplification (WGA). Moreover, white blood cells (WBC) germline contamination may confound CTC somatic mutation analyses. Thus, a good CTC enrichment platform with an efficient WGA and NGS workflow are needed. Here, Vortex label-free CTC enrichment platform was used to capture CTCs. DNA extraction was optimized, WGA evaluated and targeted NGS tested. We used metastatic colorectal cancer (CRC) as the clinical target, HCT116 as the corresponding cell line, GenomePlex® and REPLI-g as the WGA methods, GeneRead DNAseq Human CRC Panel as the 38 gene panel. The workflow was further validated on metastatic CRC patient samples, assaying both tumor and CTCs. WBCs from the same patients were included to eliminate germline contaminations. The described workflow performed well on samples with sufficient DNA, but showed bias for rare cells with limited DNA input. REPLI-g provided an unbiased amplification on fresh rare cells, enabling an accurate variant calling using the targeted NGS. Somatic variants were detected in patient CTCs and not found in age matched healthy donors. This demonstrates the feasibility of a simple workflow for clinically relevant monitoring of tumor genetics in real time and over the course of a patient’s therapy using CTCs.
The association between gene variants and longitudinal structural brain changes in psychosis: a systematic review of longitudinal neuroimaging genetics studies
Authors: Harari Julia H. , Díaz-Caneja Covadonga M. , Janssen Joost , Martínez Kenia , Arias Bárbara , Arango Celso 
Published: October 2017

AbstractEvidence suggests that genetic variation might influence structural brain alterations in psychotic disorders. Longitudinal genetic neuroimaging (G-NI) studies are designed to assess the association between genetic variants, disease progression and brain changes. There is a paucity of reviews of longitudinal G-NI studies in psychotic disorders. A systematic search of PubMed from inception until November 2016 was conducted to identify longitudinal G-NI studies examining the link between Magnetic Resonance Imaging (MRI) and Diffusion Tensor Imaging (DTI)-based brain measurements and specific gene variants (SNPs, microsatellites, haplotypes) in patients with psychosis. Eleven studies examined seven genes: BDNF, COMT, NRG1, DISC1, CNR1, GAD1, and G72. Eight of these studies reported at least one association between a specific gene variant and longitudinal structural brain changes. Genetic variants associated with longitudinal brain volume or cortical thickness loss included a 4-marker haplotype in G72, a microsatellite and a SNP in NRG1, and individual SNPs in DISC1, CNR1, BDNF, COMT and GAD1. Associations between genotype and progressive brain changes were most frequently observed in frontal regions, with five studies reporting significant interactions. Effect sizes for significant associations were generally of small or intermediate magnitude (Cohen’s d < 0.8). Only two genes (BDNF and NRG1) were assessed in more than one study, with great heterogeneity of the results. Replication studies and studies exploring additional genetic variants identified by large-scale genetic analysis are warranted to further ascertain the role of genetic variants in longitudinal brain changes in psychosis.
Hypoxia tolerance, longevity and cancer-resistance in the mole rat Spalax – a liver transcriptomics approach
Authors: Schmidt Hanno , Malik Assaf , Bicker Anne , Poetzsch Gesa , Avivi Aaron , Shams Imad , Hankeln Thomas 
Published: October 2017

AbstractThe blind subterranean mole rat Spalax shows a remarkable tolerance to hypoxia, cancer-resistance and longevity. Unravelling the genomic basis of these adaptations will be important for biomedical applications. RNA-Seq gene expression data were obtained from normoxic and hypoxic Spalax and rat liver tissue. Hypoxic Spalax broadly downregulates genes from major liver function pathways. This energy-saving response is likely a crucial adaptation to low oxygen levels. In contrast, the hypoxia-sensitive rat shows massive upregulation of energy metabolism genes. Candidate genes with plausible connections to the mole rat’s phenotype, such as important key genes related to hypoxia-tolerance, DNA damage repair, tumourigenesis and ageing, are substantially higher expressed in Spalax than in rat. Comparative liver transcriptomics highlights the importance of molecular adaptations at the gene regulatory level in Spalax and pinpoints a variety of starting points for subsequent functional studies.
Punishing second-order free riders before first-order free riders: The effect of pool punishment priority on cooperation
Authors: Ozono Hiroki , Kamijo Yoshio , Shimizu Kazumi 
Published: October 2017

AbstractSecond-order free riders, who do not owe punishment cost to first-order free riders in public goods games, lead to low cooperation. Previous studies suggest that for stable cooperation, it is critical to have a pool punishment system with second-order punishment, which gathers resources from group members and punishes second-order free riders as well as first-order free riders. In this study, we focus on the priority of punishment. We hypothesize that the pool punishment system that prioritizes second-order punishment is more likely to achieve cooperation than the system that prioritizes first-order punishment, because the former is more likely to obtain sufficient punishment resources. In the experiments, we compare four pool punishment systems: 1To2 (first-order punishment to second-order punishment), 2To1 (second-order punishment to first-order punishment), 1ONLY (first-order punishment only), and 2ONLY (second-order punishment only). We find that the 2To1 and 2ONLY systems can receive more support than the 1To2 and 1ONLY systems and only the 2To1 system can achieve high cooperation. However, the effect of priority of second-order punishment is observed only when the punishment ratio (PR) is low (Experiment 1), not high (Experiment 2), in which the punishment resource is relatively abundant.
Bioinspired Heparin Nanosponge Prepared by Photo-crosslinking for Controlled Release of Growth Factors
Authors: Choi Won Il , Sahu Abhishek , Vilos Cristian , Kamaly Nazila , Jo Seong-Min , Lee Jin Hyung , Tae Giyoong 
Published: October 2017

AbstractGrowth factors have great therapeutic potential for various disease therapy and tissue engineering applications. However, their clinical efficacy is hampered by low bioavailability, rapid degradation in vivo and non-specific biodistribution. Nanoparticle based delivery systems are being evaluated to overcome these limitations. Herein, we have developed a thermosensitive heparin nanosponge (Hep-NS) by a one step photopolymerization reaction between diacrylated pluronic and thiolated heparin molecules. The amount of heparin in Hep-NS was precisely controlled by varying the heparin amount in the reaction feed. Hep-NS with varying amounts of heparin showed similar size and shape properties, though surface charge decreased with an increase in the amount of heparin conjugation. The anticoagulant activity of the Hep-NS decreased by 65% compared to free heparin, however the Hep-NS retained their growth factor binding ability. Four different growth factors, bFGF, VEGF, BMP-2, and HGF were successfully encapsulated into Hep-NS. In vitro studies showed sustained release of all the growth factors for almost 60 days and the rate of release was directly dependent on the amount of heparin in Hep-NS. The released growth factors retained their bioactivity as assessed by a cell proliferation assay. This heparin nanosponge is therefore a promising nanocarrier for the loading and controlled release of growth factors.
Shape Controlled Synthesis of Copper Vanadate Platelet Nanostructures, Their Optical Band Edges, and Solar-Driven Water Splitting Properties
Authors: Khan Ibrahim , Qurashi Ahsanulhaq 
Published: October 2017

AbstractWe report the morphological and size tailored rational and facile synthesis of copper vanadate nanostructures via sonication assisted sol gel method. Field emission scanning electron microscopy (FESEM), indicated irregular and nanoflakes morphologies for the as synthesized copper vanadate (CV-120) and copper vanadate calcined at 250 °C (CV-250). The semispherical platelets shaped morphology revealed for the copper vanadate calcined at 550 °C (CV-500). The XRD patterns confirm the monoclinic and triclinic crystal phases for CV-250 and CV-500, respectively. The optical properties of CV-250 and CV-500 via UV-DRS showed significant absorption in the visible regime at λ = 565 nm and 670 nm with band gap 2.2 eV and 1.84 eV, respectively as calculated from Kubelka-Munk (KM) equation via Tauc’s plot. The values of band edge positions of CV-250 and CV-550 straddle with the hydrogen (HER) and oxygen evolution reaction (OER) potentials. The photoelectrodes of CV-250 and CV-500 fabricated by adsorption desorption method to test their photoelectrochemical (PEC) water splitting performance in the three-electrode cell. The onset photocurrent potential is observed at ~0.42 V, which reached to saturation at 1.05 V. The photocurrent density at saturation is ~0.65 mA/cm2 for CV-250 and CV-500, respectively.
Leishmania infantum lipophosphoglycan induced-Prostaglandin E2 production in association with PPAR-γ expression via activation of Toll like receptors-1 and 2
Authors: Lima Jonilson Berlink , Araújo-Santos Théo , Lázaro-Souza Milena , Carneiro Alan Brito , Ibraim Izabela Coimbra , Jesus-Santos Flávio Henrique , Luz Nívea Farias , Pontes Sara de Moura , Entringer Petter Franco , Descoteaux Albert , Bozza Patrícia Torres , Soares Rodrigo Pedro , Borges Valéria Matos 
Published: October 2017

AbstractLipophosphoglycan (LPG) is a key virulence factor expressed on the surfaces ofLeishmaniapromastigotes. Although LPG is known to activate macrophages, the underlying mechanisms resulting in the production of prostaglandin E2(PGE2) via signaling pathways remain unknown. Here, the inflammatory response arising from stimulation byLeishmania infantumLPG and/or its lipid and glycan motifs was evaluated with regard to PGE2induction. Intact LPG, but not its glycan and lipid moieties, induced a range of proinflammatory responses, including PGE2and nitric oxide (NO) release, increased lipid droplet formation, and iNOS and COX2 expression. LPG also induced ERK-1/2 and JNK phosphorylation in macrophages, in addition to the release of PGE2, MCP-1, IL-6, TNF-α and IL-12p70, but not IL-10. Pharmacological inhibition of ERK1/2 and PKC affected PGE2and cytokine production. Moreover, treatment with rosiglitazone, an agonist of peroxisome proliferator-activated receptor gamma (PPAR-γ), also modulated the release of PGE2and other proinflammatory mediators. Finally, we determined that LPG-induced PPAR-γ signaling occurred via TLR1/2. Taken together, these results reinforce the role played byL.infantum-derived LPG in the proinflammatory response seen inLeishmaniainfection.
Positioning of aquatic animals based on time-of-arrival and random walk models using YAPS (Yet Another Positioning Solver)
Authors: Baktoft Henrik , Gjelland Karl Øystein , Økland Finn , Thygesen Uffe Høgsbro 
Published: October 2017

AbstractAquatic positional telemetry offers vast opportunities to studyin vivobehaviour of wild animals, but there is room for improvement in the data quality provided by current procedures for estimating positions. Here we present a novel positioning method called YAPS (Yet Another Positioning Solver), involving Maximum Likelihood analysis of a state-space model applied directly to time of arrival (TOA) data in combination with a movement model. YAPS avoids the sequential positioning-filtering-approach applied in alternative tools by using all available data in a single model, and offers better accuracy and error control. Feasibility and performance of YAPS was rigorously tested in a simulation study and by applying YAPS to data from an acoustic transmitter towed in a receiver array. Performance was compared to an alternative positioning model and proprietary software. The simulation study and field test revealed that YAPS performance was better and more consistent than alternatives. We conclude that YAPS outperformed the compared alternative methods, and that YAPS constitute a vast improvement to currently available positioning software in acoustic telemetry. Additionally, in contrast to vendor-supplied solutions, YAPS is transparent, flexible and can easily be adapted and extended for further improvements or to meet study specific requirements such as three-dimensional positioning.
Proprotein convertase subtilisin/kexin type 9 (PCSK9) Deficiency is Protective Against Venous Thrombosis in Mice
Authors: Wang Hui , Wang Qian , Wang Jintao , Guo Chiao , Kleiman Kyle , Meng He , Knight Jason S. , Eitzman Daniel T. 
Published: October 2017

AbstractThe effect of lipid lowering on the incidence of deep venous thrombosis (DVT) is controversial. The purpose of this study was to determine the effect of proprotein convertase subtilisin/kexin type 9 (PCSK9) deficiency on development of DVT in mice. Pcsk9 deficient (pcsk9−/−) and wild-type (WT) littermates underwent partial inferior vena cava (IVC) ligation to induce venous thrombosis. 48 hours following IVC ligation, IVC thrombosis was evident in 60% of WT mice and 25% of pcsk9−/− mice (p < 0.05). Analysis of IVC thrombosis revealed greater thrombus weight, length, myeloid cell recruitment, and more neutrophil extracellular trap formation (NETs) in WT compared to pcsk9−/− mice. Intravital microscopy performed two hours following partial IVC ligation revealed that leukocyte firm attachment was increased in WT mice compared to mice undergoing a sham operation, however leukocyte attachment was reduced in pcsk9−/− mice compared to WT mice. In conclusion, deficiency of PCSK9 is associated with protection from venous thrombosis. This protection is associated with reduced leukocyte recruitment and NET formation at the site of thrombosis.
Shaping the evolutionary tree of green plants: evidence from the GST family
Authors: Monticolo Francesco , Colantuono Chiara , Chiusano Maria Luisa 
Published: October 2017

AbstractGlutathione-S-transferases (GSTs) are encoded by genes belonging to a wide ubiquitous family in aerobic species and catalyze the conjugation of electrophilic substrates to glutathione (GSH). GSTs are divided in different classes, both in plants and animals. In plants, GSTs function in several pathways, including those related to secondary metabolites biosynthesis, hormone homeostasis, defense from pathogens and allow the prevention and detoxification of damage from heavy metals and herbicides. 1107 GST protein sequences from 20 different plant species with sequenced genomes were analyzed. Our analysis assigns 666 unclassified GSTs proteins to specific classes, remarking the wide heterogeneity of this gene family. Moreover, we highlighted the presence of further subclasses within each class. Regarding the class GST-Tau, one possible subclass appears to be present in all the Tau members of ancestor plant species. Moreover, the results highlight the presence of members of the Tau class in Marchantiophytes and confirm previous observations on the absence of GST-Tau in Bryophytes and green algae. These results support the hypothesis regarding the paraphyletic origin of Bryophytes, but also suggest that Marchantiophytes may be on the same branch leading to superior plants, depicting an alternative model for green plants evolution.
Asymmetric Sensory-Motor Regeneration of Transected Peripheral Nerves Using Molecular Guidance Cues
Authors: Anand Sanjay , Desai Vidhi , Alsmadi Nesreen , Kanneganti Aswini , Nguyen Dianna Huyen-Tram , Tran Martin , Patil Lokesh , Vasudevan Srikanth , Xu Cancan , Hong Yi , Cheng Jonathan , Keefer Edward , Romero-Ortega Mario I. 
Published: October 2017

AbstractNeural interfaces are designed to decode motor intent and evoke sensory precepts in amputees. In peripheral nerves, recording movement intent is challenging because motor axons are only a small fraction compared to sensory fibers and are heterogeneously mixed particularly at proximal levels. We previously reported that pain and myelinated axons regenerating through a Y-shaped nerve guide with sealed ends, can be modulated by luminar release of nerve growth factor (NGF) and neurotrophin-3 (NT-3), respectively. Here, we evaluate the differential potency of NGF, glial cell line-derived neurotrophic factor (GDNF), brain-derived neurotrophic factor (BDNF), pleiotrophin (PTN), and NT-3 in asymmetrically guiding the regeneration of sensory and motor neurons. We report that, in the absence of distal target organs, molecular guidance cues can mediate the growth of electrically conductive fascicles with normal microanatomy. Compared to Y-tube compartments with bovine serum albumin (BSA), GDNF and NGF increased the motor and sensory axon content, respectively. In addition, the sensory to motor ratio was significantly increased by PTN (12.7:1) when compared to a BDNF + GDNF choice. The differential content of motor and sensory axons modulated by selective guidance cues may provide a strategy to better define axon types in peripheral nerve interfaces.
Critical controllability analysis of directed biological networks using efficient graph reduction
Authors: Ishitsuka Masayuki , Akutsu Tatsuya , Nacher Jose C. 
Published: October 2017

AbstractNetwork science has recently integrated key concepts from control theory and has applied them to the analysis of the controllability of complex networks. One of the proposed frameworks uses the Minimum Dominating Set (MDS) approach, which has been successfully applied to the identification of cancer-related proteins and in analyses of large-scale undirected networks, such as proteome-wide protein interaction networks. However, many real systems are better represented by directed networks. Therefore, fast algorithms are required for the application of MDS to directed networks. Here, we propose an algorithm that utilises efficient graph reduction to identify critical control nodes in large-scale directed complex networks. The algorithm is 176-fold faster than existing methods and increases the computable network size to 65,000 nodes. We then applied the developed algorithm to metabolic pathways consisting of 70 plant species encompassing major plant lineages ranging from algae to angiosperms and to signalling pathways from C. elegans, D. melanogaster and H. sapiens. The analysis not only identified functional pathways enriched with critical control molecules but also showed that most control categories are largely conserved across evolutionary time, from green algae and early basal plants to modern angiosperm plant lineages.
An Enhanced Platform to Analyse Low-Affinity Amyloid β Protein by Integration of Electrical Detection and Preconcentrator
Authors: Yoo Yong Kyoung , Yoon Dae Sung , Kim Gangeun , Kim Jinsik , Han Sung Il , Lee Junwoo , Chae Myung-Sic , Lee Sang-Myung , Lee Kyu Hyoung , Hwang Kyo Seon , Lee Jeong Hoon 
Published: October 2017

AbstractSensitivity and limit of detection (LOD) enhancement are essential criteria for the development of ultrasensitive molecular sensors. Although various sensor types have been investigated to enhance sensitivity and LOD, analyte detection and its quantification are still challenging, particularly for protein-protein interactions with low association constants. To solve this problem, here, we used ion concentration polarization (ICP)-based preconcentration to increase the local concentration of analytes in a microfluidic platform for LOD improvement. This was the first demonstration of a microfluidic device with an integrated ICP preconcentrator and interdigitated microelectrode (IME) sensor to detect small changes in surface binding between antigens and antibodies. We detected the amyloid beta (Aβ) protein, an Alzheimer’s disease marker, with low binding affinity to its antibodies by adopting ICP preconcentration phenomena. We demonstrated that a combination of ICP preconcentrator and IME sensor increased the LOD by 13.8-fold to femtomolar level (8.15 fM), which corresponds to a significant advance for clinical applications.
Erythropoietin Signaling Regulates Key Epigenetic and Transcription Networks in Fetal Neural Progenitor Cells
Authors: Sollinger Christina , Lillis Jacquelyn , Malik Jeffrey , Getman Michael , Proschel Chris , Steiner Laurie 
Published: October 2017

AbstractErythropoietin (EPO) and its receptor are highly expressed in the developing nervous system, and exogenous EPO therapy is potentially neuroprotective, however the epigenetic and transcriptional changes downstream of EPO signaling in neural cells are not well understood. To delineate epigenetic changes associated with EPO signaling, we compared histone H3 lysine 4 dimethylation (H3K4me2) in EPO treated and control fetal neural progenitor cells, identifying 1,150 differentially bound regions. These regions were highly enriched near protein coding genes and had significant overlap with H4Acetylation, a mark of active regulatory elements. Motif analyses and co-occupancy studies revealed a complex regulatory network underlying the differentially bound regions, including previously identified mediators of EPO signaling (STAT5, STAT3), and novel factors such as REST, an epigenetic modifier central to neural differentiation and plasticity, and NRF1, a key regulator of antioxidant response and mitochondrial biogenesis. Global transcriptome analyses on neural tubes isolated from E9.0 EpoR-null and littermate control embryos validated ourin vitrofindings, further suggesting a role for REST and NRF1 downstream of EPO signaling. These data support a role for EPO in regulating the survival, proliferation, and differentiation of neural progenitor cells, and suggest a basis for its function in neural development and neuroprotection.
Chimpanzees spontaneously take turns in a shared serial ordering task
Authors: Martin Christopher Flynn , Biro Dora , Matsuzawa Tetsuro 
Published: October 2017

AbstractSocial coordination can provide optimal solutions to many kinds of group dilemmas, and non-human subjects have been shown to perform single actions successively or simultaneously with partners to maximize food rewards in a variety of experimental settings. Less attention has been given to showing how animals are able to produce multiple (rather than single) intermixed and co-regulated actions, even though many species’ signal transmissions and social interactions rely on extended bouts of coordinated turn-taking. Here we report on coordination behaviour in three pairs of chimpanzees (mother/offspring dyads) during an experimentally induced turn-taking scenario. Participants were given a “shared” version of a computer-based serial ordering task that they had previously mastered individually. We found that minimal trial-and-error learning was necessary for the participants to solve the new social version of the task, and that information flow was more pronounced from mothers toward offspring than the reverse, mirroring characteristics of social learning in wild chimpanzees. Our experiment introduces a novel paradigm for studying behavioural coordination in non-humans, able to yield insights into the evolution of turn-taking which underlies a range of social interactions, including communication and language.