bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spontaneous emergence of fast attractor dynamics in a model of developing primary visual cortex
Authors: Miconi Thomas , McKinstry Jeffrey L. , Edelman Gerald M. 
Published: October 2016

AbstractRecent evidence suggests that neurons in primary sensory cortex arrange into competitive groups, representing stimuli by their joint activity rather than as independent feature analysers. A possible explanation for these results is that sensory cortex implements attractor dynamics, although this proposal remains controversial. Here we report that fast attractor dynamics emerge naturally in a computational model of a patch of primary visual cortex endowed with realistic plasticity (at both feedforward and lateral synapses) and mutual inhibition. When exposed to natural images (but not random pixels), the model spontaneously arranges into competitive groups of reciprocally connected, similarly tuned neurons, while developing realistic, orientation-selective receptive fields. Importantly, the same groups are observed in both stimulus-evoked and spontaneous (stimulus-absent) activity. The resulting network is inhibition-stabilized and exhibits fast, non-persistent attractor dynamics. Our results suggest that realistic plasticity, mutual inhibition and natural stimuli are jointly necessary and sufficient to generate attractor dynamics in primary sensory cortex.
Quantifying unobserved protein-coding variants in human populations provides a roadmap for large-scale sequencing projects
Authors: Zou James , Valiant Gregory , Valiant Paul , Karczewski Konrad , Chan Siu On , Samocha Kaitlin , Lek Monkol , Sunyaev Shamil , Daly Mark , MacArthur Daniel G. 
Published: October 2016

AbstractAs new proposals aim to sequence ever larger collection of humans, it is critical to have a quantitative framework to evaluate the statistical power of these projects. We developed a new algorithm, UnseenEst, and applied it to the exomes of 60,706 individuals to estimate the frequency distribution of all protein-coding variants, including rare variants that have not been observed yet in the current cohorts. Our results quantified the number of new variants that we expect to identify as sequencing cohorts reach hundreds of thousands of individuals. With 500K individuals, we find that we expect to capture 7.5% of all possible loss-of-function variants and 12% of all possible missense variants. We also estimate that 2,900 genes have loss-of-function frequency of <0.00001 in healthy humans, consistent with very strong intolerance to gene inactivation.
C14ORF39/SIX6OS1 is a constituent of the synaptonemal complex and is essential for mouse fertility
Authors: Gómez-H Laura , Felipe-Medina Natalia , Sánchez-Martín Manuel , Davies Owen R. , Ramos Isabel , García-Tuñón Ignacio , de Rooij Dirk G. , Dereli Ihsan , Tóth Attila , Barbero José Luis , Benavente Ricardo , Llano Elena , Pendas Alberto M. 
Published: October 2016

AbstractMeiotic recombination generates crossovers between homologous chromosomes that are essential for genome haploidization. The synaptonemal complex is a ‘zipper’-like protein assembly that synapses homologue pairs together and provides the structural framework for processing recombination sites into crossovers. Humans show individual differences in the number of crossovers generated across the genome. Recently, an anonymous gene variant in C14ORF39/SIX6OS1 was identified that influences the recombination rate in humans. Here we show that C14ORF39/SIX6OS1 encodes a component of the central element of the synaptonemal complex. Yeast two-hybrid analysis reveals that SIX6OS1 interacts with the well-established protein synaptonemal complex central element 1 (SYCE1). Mice lacking SIX6OS1 are defective in chromosome synapsis at meiotic prophase I, which provokes an arrest at the pachytene-like stage and results in infertility. In accordance with its role as a modifier of the human recombination rate, SIX6OS1 is essential for the appropriate processing of intermediate recombination nodules before crossover formation.
EGFR oligomerization organizes kinase-active dimers into competent signalling platforms
Authors: Needham Sarah R. , Roberts Selene K. , Arkhipov Anton , Mysore Venkatesh P. , Tynan Christopher J. , Zanetti-Domingues Laura C. , Kim Eric T. , Losasso Valeria , Korovesis Dimitrios , Hirsch Michael , Rolfe Daniel J. , Clarke David T. , Winn Martyn D. , Lajevardipour Alireza , Clayton Andrew H. A. , Pike Linda J. , Perani Michela , Parker Peter J. , Shan Yibing , Shaw David E. , Martin-Fernandez Marisa L. 
Published: October 2016

AbstractEpidermal growth factor receptor (EGFR) signalling is activated by ligand-induced receptor dimerization. Notably, ligand binding also induces EGFR oligomerization, but the structures and functions of the oligomers are poorly understood. Here, we use fluorophore localization imaging with photobleaching to probe the structure of EGFR oligomers. We find that at physiological epidermal growth factor (EGF) concentrations, EGFR assembles into oligomers, as indicated by pairwise distances of receptor-bound fluorophore-conjugated EGF ligands. The pairwise ligand distances correspond well with the predictions of our structural model of the oligomers constructed from molecular dynamics simulations. The model suggests that oligomerization is mediated extracellularly by unoccupied ligand-binding sites and that oligomerization organizes kinase-active dimers in ways optimal for auto-phosphorylation in trans between neighbouring dimers. We argue that ligand-induced oligomerization is essential to the regulation of EGFR signalling.
Plants capable of selfing are more likely to become naturalized
Authors: Razanajatovo Mialy , Maurel Noëlie , Dawson Wayne , Essl Franz , Kreft Holger , Pergl Jan , Pyšek Petr , Weigelt Patrick , Winter Marten , van Kleunen Mark 
Published: October 2016

AbstractMany plant species have established self-sustaining populations outside their natural range because of human activities. Plants with selfing ability should be more likely to establish outside their historical range because they can reproduce from a single individual when mates or pollinators are not available. Here, we compile a global breeding-system database of 1,752 angiosperm species and use phylogenetic generalized linear models and path analyses to test relationships between selfing ability, life history, native range size and global naturalization status. Selfing ability is associated with annual or biennial life history and a large native range, which both positively correlate with the probability of naturalization. Path analysis suggests that a high selfing ability directly increases the number of regions where a species is naturalized. Our results provide robust evidence across flowering plants at the global scale that high selfing ability fosters alien plant naturalization both directly and indirectly.
Room-temperature Tamm-plasmon exciton-polaritons with a WSe2 monolayer
Authors: Lundt Nils , Klembt Sebastian , Cherotchenko Evgeniia , Betzold Simon , Iff Oliver , Nalitov Anton V. , Klaas Martin , Dietrich Christof P. , Kavokin Alexey V. , Höfling Sven , Schneider Christian 
Published: October 2016

AbstractSolid-state cavity quantum electrodynamics is a rapidly advancing field, which explores the frontiers of light–matter coupling. Metal-based approaches are of particular interest in this field, as they carry the potential to squeeze optical modes to spaces significantly below the diffraction limit. Transition metal dichalcogenides are ideally suited as the active material in cavity quantum electrodynamics, as they interact strongly with light at the ultimate monolayer limit. Here, we implement a Tamm-plasmon-polariton structure and study the coupling to a monolayer of WSe2, hosting highly stable excitons. Exciton-polariton formation at room temperature is manifested in the characteristic energy–momentum dispersion relation studied in photoluminescence, featuring an anti-crossing between the exciton and photon modes with a Rabi-splitting of 23.5 meV. Creating polaritonic quasiparticles in monolithic, compact architectures with atomic monolayers under ambient conditions is a crucial step towards the exploration of nonlinearities, macroscopic coherence and advanced spinor physics with novel, low-mass bosons.
Graphene-coated meshes for electroactive flow control devices utilizing two antagonistic functions of repellency and permeability
Authors: Tabassian Rassoul , Oh Jung-Hwan , Kim Sooyeun , Kim Donggyu , Ryu Seunghwa , Cho Seung-Min , Koratkar Nikhil , Oh Il-Kwon 
Published: October 2016

AbstractThe wettability of graphene on various substrates has been intensively investigated for practical applications including surgical and medical tools, textiles, water harvesting, self-cleaning, oil spill removal and microfluidic devices. However, most previous studies have been limited to investigating the intrinsic and passive wettability of graphene and graphene hybrid composites. Here, we report the electrowetting of graphene-coated metal meshes for use as electroactive flow control devices, utilizing two antagonistic functions, hydrophobic repellency versus liquid permeability. Graphene coating was able to prevent the thermal oxidation and corrosion problems that plague unprotected metal meshes, while also maintaining its hydrophobicity. The shapes of liquid droplets and the degree of water penetration through the graphene-coated meshes were controlled by electrical stimuli based on the functional control of hydrophobic repellency and liquid permeability. Furthermore, using the graphene-coated metal meshes, we developed two active flow devices demonstrating the dynamic locomotion of water droplets and electroactive flow switching.
Constitutively activated PI3K accelerates tumor initiation and modifies histopathology of breast cancer
Authors: Sheen M R , Marotti J D , Allegrezza M J , Rutkowski M , Conejo-Garcia J R , Fiering S 
Published: October 2016

AbstractThe gene encoding phosphatidylinositol 3-kinase catalytic subunit α-isoform (PIK3CA, p110α) is frequently activated by mutation in human cancers. Based on detection in some breast cancer precursors, PIK3CA mutations have been proposed to have a role in tumor initiation. To investigate this hypothesis, we generated a novel mouse model with a Cre-recombinase regulated allele of p110α (myristoylated-p110α, myr-p110α) along with p53fl/fl deletion and KrasG12D also regulated by Cre-recombinase. After instillation of adenovirus-expressing Cre-recombinase into mammary ducts, we found that myr-p110α accelerated breast tumor initiation in a copy number-dependent manner. Breast tumors induced by p53fl/fl;KrasG12D with no or one copy of myr-p110α had predominantly sarcomatoid features, whereas two copies of myr-p110α resulted in tumors with a carcinoma phenotype. This novel model provides experimental support for importance of active p110α in breast tumor initiation, and shows that the amount of PI3K activity can affect the rate of tumor initiation and modify the histological phenotype of breast cancer.
Rapid and sustained cognitive recovery in APP/PS1 transgenic mice by co-administration of EPPS and donepezil
Authors: Kim Hye Yun , Kim Hyunjin Vincent , Lee Dongkeun K. , Yang Seung-Hoon , Kim YoungSoo 
Published: October 2016

AbstractAlzheimer’s disease (AD) is a neurodegenerative disease characterized by sequential progression of pathological events, such as aggregation of amyloid-β proteins, followed by outward symptoms of cognitive impairments. Given that a combination of different therapeutic strategies often provides more rapid and effective outcomes in diverse areas of clinical treatment, we hypothesized that administration of anti-amyloid drugs with cognitive enhancers would result in synergistic effects in AD treatment. Here, we co-administered 4-(2-hydroxyethyl)-1-piperazinepropane-sulphonic acid (EPPS), an amyloid-clearing chemical, and donepezil, an acetylcholinesterase inhibitor, to determine whether they could serve complementary roles for each other in regards to AD treatment. We found that oral administration of these two molecules led to a rapid and consistent cognitive improvement in APP/PS1 transgenic mice. Although there was no evidence for synergistic effects, our results indicated that EPPS and donepezil function complementary to each other without altering their individual effects. Thus, the combined use of disease-modifying and symptomatic relief drugs may be a promising approach in the treatment of AD.
An extract from Taxodium distichum targets hemagglutinin- and neuraminidase-related activities of influenza virus in vitro
Authors: Hsieh Chung-Fan , Chen Yu-Li , Lin Chwan-Fwu , Ho Jin-Yuan , Huang Chun-Hsun , Chiu Cheng-Hsun , Hsieh Pei-Wen , Horng Jim-Tong 
Published: October 2016

AbstractInfluenza virus remains an emerging virus and causes pandemics with high levels of fatality. After screening different plant extracts with potential anti-influenza activity, a water extract of Taxodium distichum stems (TDSWex) showed excellent activity against influenza viruses. The EC50 of TDSWex was 0.051 ± 0.024 mg/mL against influenza virus A/WSN/33. TDSWex had excellent antiviral efficacy against various strains of human influenza A and B viruses, particularly oseltamivir-resistant clinical isolates and a swine-origin influenza strain. We observed that the synthesis of viral RNA and protein were inhibited in the presence of TDSWex. The results of the time-of-addition assay suggested that TDSWex inhibited viral entry and budding. In the hemagglutination inhibition assay, TDSWex inhibited the hemagglutination of red blood cells, implying that the extract targeted hemagglutin-related functions such as viral entry. In the attachment and penetration assay, TDSWex showed antiviral activity with EC50s of 0.045 ± 0.026 and 0.012 ± 0.003 mg/mL, respectively. In addition, TDSWex blocked neuraminidase activity. We conclude that TDSWex has bimodal activities against both hemagglutinin and neuraminidase during viral replication.
Disease-mediated bottom-up regulation: An emergent virus affects a keystone prey, and alters the dynamics of trophic webs
Authors: Monterroso Pedro , Garrote Germán , Serronha Ana , Santos Emídio , Delibes-Mateos Miguel , Abrantes Joana , Perez de Ayala Ramón , Silvestre Fernando , Carvalho João , Vasco Inês , Lopes Ana M. , Maio Elisa , Magalhães Maria J. , Mills L. Scott , Esteves Pedro J. , Simón Miguel Ángel , Alves Paulo C. 
Published: October 2016

AbstractEmergent diseases may alter the structure and functioning of ecosystems by creating new biotic interactions and modifying existing ones, producing cascading processes along trophic webs. Recently, a new variant of the rabbit haemorrhagic disease virus (RHDV2 or RHDVb) arguably caused widespread declines in a keystone prey in Mediterranean ecosystems - the European rabbit (Oryctolagus cuniculus). We quantitatively assess the impact of RHDV2 on natural rabbit populations and in two endangered apex predator populations: the Iberian lynx (Lynx pardinus) and the Spanish Imperial eagle (Aquila adalberti). We found 60–70% declines in rabbit populations, followed by decreases of 65.7% in Iberian lynx and 45.5% in Spanish Imperial eagle fecundities. A revision of the web of trophic interactions among rabbits and their dependent predators suggests that RHDV2 acts as a keystone species, and may steer Mediterranean ecosystems to management-dependent alternative states, dominated by simplified mesopredator communities. This model system stresses the importance of diseases as functional players in the dynamics of trophic webs.
Ductular reaction-on-a-chip: Microfluidic co-cultures to study stem cell fate selection during liver injury
Authors: Haque Amranul , Gheibi Pantea , Stybayeva Gulnaz , Gao Yandong , Torok Natalie , Revzin Alexander 
Published: October 2016

AbstractLiver injury modulates local microenvironment, triggering production of signals that instruct stem cell fate choices. In this study, we employed a microfluidic co-culture system to recreate important interactions in the liver stem cell niche, those between adult hepatocytes and liver progenitor cells (LPCs). We demonstrate that pluripotent stem cell-derived LPCs choose hepatic fate when cultured next to healthy hepatocytes but begin biliary differentiation program when co-cultured with injured hepatocytes. We connect this fate selection to skewing in production of hepatocyte growth factor (HGF) and transforming growth factor (TGF)-β1 caused by injury. Significantly, biliary fate selection of LPCs was not observed in the absence of hepatocytes nor did it happen in the presence of TGF-β inhibitors. Our study demonstrates that microfluidic culture systems may offer an interesting new tool for dissecting cellular interactions leading to aberrant stem cell differentiation during injury.
Alpha-enolase on apical surface of renal tubular epithelial cells serves as a calcium oxalate crystal receptor
Authors: Fong-ngern Kedsarin , Thongboonkerd Visith 
Published: October 2016

AbstractTo search for a strategy to prevent kidney stone formation/recurrence, this study addressed the role of α-enolase on apical membrane of renal tubular cells in mediating calcium oxalate monohydrate (COM) crystal adhesion. Its presence on apical membrane and in COM crystal-bound fraction was confirmed by Western blotting and immunofluorescence staining. Pretreating MDCK cells with anti-α-enolase antibody, not isotype-controlled IgG, dramatically reduced cell-crystal adhesion. Immunofluorescence staining also confirmed the direct binding of purified α-enolase to COM crystals at {121} > {100} > {010} crystal faces. Coating COM crystals with urinary proteins diminished the crystal binding capacity to cells and purified α-enolase. Moreover, α-enolase selectively bound to COM, not other crystals. Chemico-protein interactions analysis revealed that α-enolase interacted directly with Ca2+ and Mg2+. Incubating the cells with Mg2+ prior to cell-crystal adhesion assay significantly reduced crystal binding on the cell surface, whereas preincubation with EDTA, a divalent cation chelator, completely abolished Mg2+ effect, indicating that COM and Mg2+ competitively bind to α-enolase. Taken together, we successfully confirmed the role of α-enolase as a COM crystal receptor to mediate COM crystal adhesion at apical membrane of renal tubular cells. It may also serve as a target for stone prevention by blocking cell-crystal adhesion and stone nidus formation.
GigaGauss solenoidal magnetic field inside bubbles excited in under-dense plasma
Authors: Lécz Zs. , Konoplev I. V. , Seryi A. , Andreev A. 
Published: October 2016

AbstractThis paper proposes a novel and effective method for generating GigaGauss level, solenoidal quasi-static magnetic fields in under-dense plasma using screw-shaped high intensity laser pulses. This method produces large solenoidal fields that move with the driving laser pulse and are collinear with the accelerated electrons. This is in contrast with already known techniques which rely on interactions with over-dense or solid targets and generates radial or toroidal magnetic field localized at the stationary target. The solenoidal field is quasi-stationary in the reference frame of the laser pulse and can be used for guiding electron beams. It can also provide synchrotron radiation beam emittance cooling for laser-plasma accelerated electron and positron beams, opening up novel opportunities for designs of the light sources, free electron lasers, and high energy colliders based on laser plasma acceleration.
Heme-mediated apoptosis and fusion damage in BeWo trophoblast cells
Authors: Liu Mingli , Hassana Salifu , Stiles Jonathan K. 
Published: October 2016

AbstractPlacental malaria (PM) is a complication associated with malaria infection during pregnancy that often leads to abortion, premature delivery, intrauterine growth restriction and low birth weight. Increased levels of circulating free heme, a by-product of Plasmodium-damaged erythrocytes, is a major contributor to inflammation, tissue damage and loss of blood brain barrier integrity associated with fatal experimental cerebral malaria. However, the role of heme in PM remains unknown. Proliferation and apoptosis of trophoblasts and fusion of the mononucleated state to the syncytial state are of major importance to a successful pregnancy. In the present study, we examined the effects of heme on the viability and fusion of a trophoblast-derived cell line (BeWo). Results indicate that heme induces apoptosis in BeWo cells by activation of the STAT3/caspase-3/PARP signaling pathway. In the presence of forskolin, which triggers trophoblast fusion, heme inhibits BeWo cell fusion through activation of STAT3. Understanding the effects of free plasma heme in pregnant women either due to malaria, sickle cell disease or other hemolytic diseases, will enable identification of high-risk women and may lead to discovery of new drug targets against associated adverse pregnancy outcome.
Antagonistic autoregulation speeds up a homogeneous response in Escherichia coli
Authors: Rodrigo Guillermo , Bajic Djordje , Elola Ignacio , Poyatos Juan F. 
Published: October 2016

AbstractBy integrating positive and negative feedback loops, biological systems establish intricate gene expression patterns linked to multistability, pulsing, and oscillations. This depends on the specific characteristics of each interlinked feedback, and thus one would expect additional expression programs to be found. Here, we investigate one such program associated with an antagonistic positive and negative transcriptional autoregulatory motif derived from the multiple antibiotic resistance (mar) system of Escherichia coli. We studied the dynamics of the system by combining a predictive mathematical model with high-resolution experimental measures of the response both at the population and single-cell level. We show that in this motif the weak positive autoregulation does not slow down but rather enhances response speedup in combination with a strong negative feedback loop. This balance of feedback strengths anticipates a homogeneous population phenotype, which we corroborate experimentally. Theoretical analysis also emphasized the specific molecular properties that determine the dynamics of the mar phenotype. More broadly, response acceleration could provide a rationale for the presence of weak positive feedbacks in other biological scenarios exhibiting these interlinked regulatory architectures.
Odor-induced mood state modulates language comprehension by affecting processing strategies
Authors: Wang Lin , Zhou Bin , Zhou Wen , Yang Yufang 
Published: October 2016

AbstractIt is controversial whether mood affects cognition by triggering specific processing strategies or by limiting processing resources. The current event-related potential (ERP) study pursued this issue by examining how mood modulates the processing of task relevant/irrelevant information. In question-answer pairs, a question context marked a critical word in the answer sentence as focus (and thus relevant) or non-focus (thereby irrelevant). At the same time, participants were exposed to either a pleasant or unpleasant odor to elicit different mood states. Overall, we observed larger N400s when the critical words in the answer sentences were semantically incongruent (rather than congruent) with the question context. However, such N400 effect was only found for focused words accompanied by a pleasant odor and for both focused and non-focused words accompanied by an unpleasant odor, but not for non-focused words accompanied by a pleasant odor. These results indicate top-down attentional shift to the focused information in a positive mood state and non-selective attention allocated to the focused and non-focused information in a less positive mood state, lending support to the “processing strategy” hypothesis. By using a novel approach to induce mood states, our study provides fresh insights into the mechanisms underlying mood modulation of language comprehension.