bluuebunny/crossref_metadata_2025_split huggingface dataset:
Electrophysiological dynamics of Chinese phonology during visual word recognition in Chinese-English bilinguals
Authors: Wen Yun , Filik Ruth , van Heuven Walter J. B. 
Published: April 2018

AbstractSilent word reading leads to the activation of orthographic (spelling), semantic (meaning), as well as phonological (sound) information. For bilinguals, native language information can also be activated automatically when they read words in their second language. For example, when Chinese-English bilinguals read words in their second language (English), the phonology of the Chinese translations is automatically activated. Chinese phonology, however, consists of consonants and vowels (segmental) and tonal information. To what extent these two aspects of Chinese phonology are activated is yet unclear. Here, we used behavioural measures, event-related potentials and oscillatory EEG to investigate Chinese segmental and tonal activation during word recognition. Evidence of Chinese segmental activation was found when bilinguals read English words (faster responses, reduced N400, gamma-band power reduction) and when they read Chinese words (increased LPC, gamma-band power reduction). In contrast, evidence for Chinese tonal activation was only found when bilinguals read Chinese words (gamma-band power increase). Together, our converging behavioural and electrophysiological evidence indicates that Chinese segmental information is activated during English word reading, whereas both segmental and tonal information are activated during Chinese word reading. Importantly, gamma-band oscillations are modulated differently by tonal and segmental activation, suggesting independent processing of Chinese tones and segments.
Preparatory activity for purposeful arm movements in the dorsomedial parietal area V6A: Beyond the online guidance of movement
Authors: Santandrea Elisa , Breveglieri Rossella , Bosco Annalisa , Galletti Claudio , Fattori Patrizia 
Published: April 2018

AbstractOver the years, electrophysiological recordings in macaque monkeys performing visuomotor tasks brought about accumulating evidence for the expression of neuronal properties (e.g., selectivity in the visuospatial and somatosensory domains, encoding of visual affordances and motor cues) in the posterior parietal area V6A that characterize it as an ideal neural substrate for online control of prehension. Interestingly, neuroimaging studies suggested a role of putative human V6A also in action preparation; moreover, pre-movement population activity in monkey V6A has been recently shown to convey grip-related information for upcoming grasping. Here we directly test whether macaque V6A neurons encode preparatory signals that effectively differentiate between dissimilar actions before movement. We recorded the activity of single V6A neurons during execution of two visuomotor tasks requiring either reach-to-press or reach-to-grasp movements in different background conditions, and described the nature and temporal dynamics of V6A activity preceding movement execution. We found striking consistency in neural discharges measured during pre-movement and movement epochs, suggesting that the former is a preparatory activity exquisitely linked to the subsequent execution of particular motor actions. These findings strongly support a role of V6A beyond the online guidance of movement, with preparatory activity implementing suitable motor programs that subsequently support action execution.
(Poly)phenol-digested metabolites modulate alpha-synuclein toxicity by regulating proteostasis
Authors: Macedo Diana , Jardim Carolina , Figueira Inês , Almeida A. Filipa , McDougall Gordon J. , Stewart Derek , Yuste Jose E. , Tomás-Barberán Francisco A. , Tenreiro Sandra , Outeiro Tiago F. , Santos Cláudia N. 
Published: April 2018

AbstractParkinson’s disease (PD) is an age-related neurodegenerative disease associated with the misfolding and aggregation of alpha-synuclein (aSyn). The molecular underpinnings of PD are still obscure, but nutrition may play an important role in the prevention, onset, and disease progression. Dietary (poly)phenols revert and prevent age-related cognitive decline and neurodegeneration in model systems. However, only limited attempts were made to evaluate the impact of digestion on the bioactivities of (poly)phenols and determine their mechanisms of action. This constitutes a challenge for the development of (poly)phenol-based nutritional therapies. Here, we subjected (poly)phenols from Arbutus unedo to in vitro digestion and tested the products in cell models of PD based on the cytotoxicity of aSyn. The (poly)phenol-digested metabolites from A. unedo leaves (LPDMs) effectively counteracted aSyn and H2O2 toxicity in yeast and human cells, improving viability by reducing aSyn aggregation and inducing its clearance. In addition, LPDMs modulated pathways associated with aSyn toxicity, such as oxidative stress, endoplasmic reticulum (ER) stress, mitochondrial impairment, and SIR2 expression. Overall, LPDMs reduced aSyn toxicity, enhanced the efficiency of ER-associated protein degradation by the proteasome and autophagy, and reduced oxidative stress. In total, our study opens novel avenues for the exploitation of (poly)phenols in nutrition and health.
Development of a generic β-lactamase screening system for improved signal peptides for periplasmic targeting of recombinant proteins in Escherichia coli
Authors: Selas Castiñeiras Tania , Williams Steven G. , Hitchcock Antony , Cole Jeffrey A. , Smith Daniel C. , Overton Tim W. 
Published: April 2018

AbstractTargeting of recombinant proteins to the Escherichia coli periplasm is a desirable industrial processing tool to allow formation of disulphide bonds, aid folding and simplify recovery. Proteins are targeted across the inner membrane to the periplasm by an N-terminal signal peptide. The sequence of the signal peptide determines its functionality, but there is no method to predict signal peptide function for specific recombinant proteins, so multiple signal peptides must be screened for their ability to translocate each recombinant protein, limiting throughput. We present a screening system for optimising signal peptides for translocation of a single chain variable (scFv) antibody fragment employing TEM1 β-lactamase (Bla) as a C-terminal reporter of periplasmic localisation. The Pectobacterium carotovorum PelB signal peptide was selected as the starting point for a mutagenic screen. β-lactamase was fused to the C-terminal of scFv and β-lactamase activity was correlated against scFv translocation. Signal peptide libraries were generated and screened for β-lactamase activity, which correlated well to scFv::Bla production, although only some high activity clones had improved periplasmic translocation of scFv::Bla. Selected signal peptides were investigated in fed-batch fermentations for production and translocation of scFv::Bla and scFv without the Bla fusion. Improved signal peptides increased periplasmic scFv activity by ~40%.
Drosophila Voltage-Gated Calcium Channel α1-Subunits Regulate Cardiac Function in the Aging Heart
Authors: Lam Alexander , Karekar Priyanka , Shah Kajol , Hariharan Girija , Fleyshman Michelle , Kaur Harmehak , Singh Harpreet , Gururaja Rao Shubha 
Published: April 2018

AbstractIon channels maintain numerous physiological functions and regulate signaling pathways. They are the key targets for cellular reactive oxygen species (ROS), acting as signaling switches between ROS and ionic homeostasis. We have carried out a paraquat (PQ) screen in Drosophila to identify ion channels regulating the ROS handling and survival in Drosophila melanogaster. Our screen has revealed that α1-subunits (D-type, T-type, and cacophony) of voltage-gated calcium channels (VGCCs) handle PQ-mediated ROS stress differentially in a gender-based manner. Since ROS are also involved in determining the lifespan, we discovered that the absence of T-type and cacophony decreased the lifespan while the absence of D-type maintained a similar lifespan to that of the wild-type strain. VGCCs are also responsible for electrical signaling in cardiac cells. The cardiac function of each mutant was evaluated through optical coherence tomography (OCT), which revealed that α1-subunits of VGCCs are essential in maintaining cardiac rhythmicity and cardiac function in an age-dependent manner. Our results establish specific roles of α1-subunits of VGCCs in the functioning of the aging heart.
Modulation of Haemophilus influenzae interaction with hydrophobic molecules by the VacJ/MlaA lipoprotein impacts strongly on its interplay with the airways
Authors: Fernández-Calvet Ariadna , Rodríguez-Arce Irene , Almagro Goizeder , Moleres Javier , Euba Begoña , Caballero Lucía , Martí Sara , Ramos-Vivas José , Bartholomew Toby Leigh , Morales Xabier , Ortíz-de-Solórzano Carlos , Yuste José Enrique , Bengoechea José Antonio , Conde-Álvarez Raquel , Garmendia Junkal 
Published: April 2018

AbstractAirway infection by nontypeable Haemophilus influenzae (NTHi) associates to chronic obstructive pulmonary disease (COPD) exacerbation and asthma neutrophilic airway inflammation. Lipids are key inflammatory mediators in these disease conditions and consequently, NTHi may encounter free fatty acids during airway persistence. However, molecular information on the interplay NTHi-free fatty acids is limited, and we lack evidence on the importance of such interaction to infection. Maintenance of the outer membrane lipid asymmetry may play an essential role in NTHi barrier function and interaction with hydrophobic molecules. VacJ/MlaA-MlaBCDEF prevents phospholipid accumulation at the bacterial surface, being the only system involved in maintaining membrane asymmetry identified in NTHi. We assessed the relationship among the NTHi VacJ/MlaA outer membrane lipoprotein, bacterial and exogenous fatty acids, and respiratory infection. The vacJ/mlaA gene inactivation increased NTHi fatty acid and phospholipid global content and fatty acyl specific species, which in turn increased bacterial susceptibility to hydrophobic antimicrobials, decreased NTHi epithelial infection, and increased clearance during pulmonary infection in mice with both normal lung function and emphysema, maybe related to their shared lung fatty acid profiles. Altogether, we provide evidence for VacJ/MlaA as a key bacterial factor modulating NTHi survival at the human airway upon exposure to hydrophobic molecules.
Wolbachia significantly impacts the vector competence of Aedes aegypti for Mayaro virus
Authors: Pereira Thiago Nunes , Rocha Marcele Neves , Sucupira Pedro Henrique Ferreira , Carvalho Fabiano Duarte , Moreira Luciano Andrade 
Published: April 2018

AbstractWolbachia, an intracellular endosymbiont present in up to 70% of all insect species, has been suggested as a sustainable strategy for the control of arboviruses such as Dengue, Zika and Chikungunya. As Mayaro virus outbreaks have also been reported in Latin American countries, the objective of this study was to evaluate the vector competence of Brazilian field-collected Ae. aegypti and the impact of Wolbachia (wMel strain) upon this virus. Our in vitro studies with Aag2 cells showed that Mayaro virus can rapidly multiply, whereas in wMel-infected Aag2 cells, viral growth was significantly impaired. In addition, C6/36 cells seem to have alterations when infected by Mayaro virus. In vivo experiments showed that field-collected Ae. aegypti mosquitoes are highly permissive to Mayaro virus infection, and high viral prevalence was observed in the saliva. On the other hand, Wolbachia-harboring mosquitoes showed significantly impaired capability to transmit Mayaro virus. Our results suggest that the use of Wolbachia-harboring mosquitoes may represent an effective mechanism for the reduction of Mayaro virus transmission throughout Latin America.
Compound heterozygous TYK2 mutations underlie primary immunodeficiency with T-cell lymphopenia
Authors: Nemoto Michiko , Hattori Hiroyoshi , Maeda Naoko , Akita Nobuhiro , Muramatsu Hideki , Moritani Suzuko , Kawasaki Tomonori , Maejima Masami , Ode Hirotaka , Hachiya Atsuko , Sugiura Wataru , Yokomaku Yoshiyuki , Horibe Keizo , Iwatani Yasumasa 
Published: April 2018

AbstractComplete tyrosine kinase 2 (TYK2) deficiency has been previously described in patients with primary immunodeficiency diseases. The patients were infected with various pathogens, including mycobacteria and/or viruses, and one of the patients developed hyper-IgE syndrome. A detailed immunological investigation of these patients revealed impaired responses to type I IFN, IL-10, IL-12 and IL-23, which are associated with increased susceptibility to mycobacterial and/or viral infections. Herein, we report a recessive partial TYK2 deficiency in two siblings who presented with T-cell lymphopenia characterized by low naïve CD4+ T-cell counts and who developed Epstein-Barr virus (EBV)-associated B-cell lymphoma. Targeted exome-sequencing of the siblings’ genomes demonstrated that both patients carried novel compound heterozygous mutations (c.209_212delGCTT/c.691C > T, p.Cys70Serfs*21/p.Arg231Trp) in the TYK2. The TYK2 protein levels were reduced by 35% in the T cells of the patient. Unlike the response under complete TYK2 deficiency, the patient’s T cells responded normally to type I IFN, IL-6, IL-10 and IL-12, whereas the cells displayed an impaired response to IL-23. Furthermore, the level of STAT1 was low in the cells of the patient. These studies reveal a new clinical entity of a primary immunodeficiency with T-cell lymphopenia that is associated with compound heterozygous TYK2 mutations in the patients.
Isothermal folding of a light-up bio-orthogonal RNA origami nanoribbon
Authors: Torelli Emanuela , Kozyra Jerzy Wieslaw , Gu Jing-Ying , Stimming Ulrich , Piantanida Luca , Voïtchovsky Kislon , Krasnogor Natalio 
Published: April 2018

AbstractRNA presents intringuing roles in many cellular processes and its versatility underpins many different applications in synthetic biology. Nonetheless, RNA origami as a method for nanofabrication is not yet fully explored and the majority of RNA nanostructures are based on natural pre-folded RNA. Here we describe a biologically inert and uniquely addressable RNA origami scaffold that self-assembles into a nanoribbon by seven staple strands. An algorithm is applied to generate a synthetic De Bruijn scaffold sequence that is characterized by the lack of biologically active sites and repetitions larger than a predetermined design parameter. This RNA scaffold and the complementary staples fold in a physiologically compatible isothermal condition. In order to monitor the folding, we designed a new split Broccoli aptamer system. The aptamer is divided into two nonfunctional sequences each of which is integrated into the 5′ or 3′ end of two staple strands complementary to the RNA scaffold. Using fluorescence measurements and in-gel imaging, we demonstrate that once RNA origami assembly occurs, the split aptamer sequences are brought into close proximity forming the aptamer and turning on the fluorescence. This light-up ‘bio-orthogonal’ RNA origami provides a prototype that can have potential for in vivo origami applications.
Exploring Leptospiral proteomes to identify potential candidates for vaccine design against Leptospirosis using an immunoinformatics approach
Authors: Lata Kumari Snehkant , Kumar Swapnil , Vaghasia Vibhisha , Sharma Priyanka , Bhairappanvar Shivarudrappa B. , Soni Subhash , Das Jayashankar 
Published: April 2018

AbstractLeptospirosis is the most widespread zoonotic disease, estimated to cause severe infection in more than one million people each year, particularly in developing countries of tropical areas. Several factors such as variable and nonspecific clinical manifestation, existence of large number of serovars and asymptomatic hosts spreading infection, poor sanitation and lack of an effective vaccine make prophylaxis difficult. Consequently, there is an urgent need to develop an effective vaccine to halt its spread all over the world. In this study, an immunoinformatics approach was employed to identify the most vital and effective immunogenic protein from the proteome ofLeptospira interrogansserovar Copenhageni strain L1-130 that may be suitable to stimulate a significant immune response aiding in the development of peptide vaccine against leptospirosis. Both B-cell and T-cell (Helper T-lymphocyte (HTL) and cytotoxic T lymphocyte (CTL)) epitopes were predicted for the conserved and most immunogenic outer membrane lipoprotein. Further, the binding interaction of CTL epitopes with Major Histocompatibility Complex class I (MHC-I) was evaluated using docking techniques. A Molecular Dynamics Simulation study was also performed to evaluate the stability of the resulting epitope-MHC-I complexes. Overall, this study provides novel vaccine candidates and may prompt further development of vaccines against leptospirosis.
Effects of precipitates and dislocation loops on the yield stress of irradiated iron
Authors: Lehtinen Arttu , Laurson Lasse , Granberg Fredric , Nordlund Kai , Alava Mikko J. 
Published: April 2018

AbstractPlastic deformation of crystalline materials is governed by the features of stress-driven motion of dislocations. In the case of irradiated steels subject to applied stresses, small dislocation loops as well as precipitates are known to interfere with the dislocation motion, leading to an increased yield stress as compared to pure crystals. We study the combined effect of precipitates and interstitial glissile $$\frac{{\bf{1}}}{{\bf{2}}}\langle {\bf{111}}\rangle $$

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2

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dislocation loops on the yield stress of iron, using large-scale three-dimensional discrete dislocation dynamics simulations. Precipitates are included in the simulations using our recent multi-scale implementation [A. Lehtinen et al., Phys. Rev. E 93 (2016) 013309], where the strengths and pinning mechanisms of the precipitates are determined from molecular dynamics simulations. In the simulations we observe dislocations overcoming precipitates with an atypical Orowan mechanism which results from pencil-glide of screw segments in iron. Even if the interaction mechanisms with dislocations are quite different, our results suggest that in relative terms, precipitates and loops of similar sizes contribute equally to the yield stress in multi-slip conditions.
Characterizing the role of atrial natriuretic peptide signaling in the development of embryonic ventricular conduction system
Authors: Govindapillai Arun , Hotchkiss Adam , Baguma-Nibasheka Mark , Rose Robert A. , Miquerol Lucile , Smithies Oliver , Maeda Nobuyo , Pasumarthi Kishore B. S. 
Published: April 2018

AbstractPatients born with congenital heart defects frequently encounter arrhythmias due to defects in the ventricular conduction system (VCS) development. Although recent studies identified transcriptional networks essential for the heart development, there is scant information on the mechanisms regulating VCS development. Based on the association of atrial natriuretic peptide (ANP) expression with VCS forming regions, it was reasoned that ANP could play a critical role in differentiation of cardiac progenitor cells (CPCs) and cardiomyocytes (CMs) toward a VCS cell lineage. The present study showed that treatment of embryonic ventricular cells with ANP or cell permeable 8-Br-cGMP can induce gene expression of important VCS markers such as hyperpolarization-activated cyclic nucleotide-gated channel-4 (HCN4) and connexin 40 (Cx40). Inhibition of protein kinase G (PKG) via Rp-8-pCPT-cGMPS further confirmed the role of ANP/NPRA/cGMP/PKG pathway in the regulation of HCN4 and Cx40 gene expression. Additional experiments indicated that ANP may regulate VCS marker gene expression by modulating levels of miRNAs that are known to control the stability of transcripts encoding HCN4 and Cx40. Genetic ablation of NPRA revealed significant decreases in VCS marker gene expression and defects in Purkinje fiber arborisation. These results provide mechanistic insights into the role of ANP/NPRA signaling in VCS formation.
mTOR complexes differentially orchestrates eosinophil development in allergy
Authors: Zhu Chen , Xia Lixia , Li Fei , Zhou Lingren , Weng Qingyu , Li Zhouyang , Wu Yinfang , Mao Yuanyuan , Zhang Chao , Wu Yanping , Li Miao , Ying Songmin , Chen Zhihua , Shen Huahao , Li Wen 
Published: April 2018

AbstractEosinophil infiltration is considered a hallmark in allergic airway inflammation, and the blockade of eosinophil differentiation may be an effective approach for treating eosinophil-related disorders. Mammalian target of rapamycin (mTOR) is a vital modulator in cell growth control and related diseases, and we have recently demonstrated that rapamycin can suppress eosinophil differentiation in allergic airway inflammation. Considering its critical role in haematopoiesis, we further investigated the role of mTOR in eosinophil differentiation in the context of asthmatic pathogenesis. Intriguingly, the inhibition of mTOR, either by genetic deletion or by another pharmacological inhibitor torin-1, accelerated the eosinophil development in the presence of IL-5. However, this was not observed to have any considerable effect on eosinophil apoptosis. The effect of mTOR in eosinophil differentiation was mediated by Erk signalling. Moreover, myeloid specific knockout of mTOR or Rheb further augmented allergic airway inflammation in mice after allergen exposure. Ablation of mTOR in myeloid cells also resulted in an increased number of eosinophil lineage-committed progenitors (Eops) in allergic mice. Collectively, our data uncovered the differential effects of mTOR in the regulation of eosinophil development, likely due to the distinct functions of mTOR complex 1 or 2, which thus exerts a pivotal implication in eosinophil-associated diseases.
The acoustic adaptation hypothesis in a widely distributed South American frog: Southernmost signals propagate better
Authors: Velásquez Nelson A. , Moreno-Gómez Felipe N. , Brunetti Enzo , Penna Mario 
Published: April 2018

AbstractAnimal communication occurs in environments that affect the properties of signals as they propagate from senders to receivers. We studied the geographic variation of the advertisement calls of male Pleurodema thaul individuals from eight localities in Chile. Furthermore, by means of signal propagation experiments, we tested the hypothesis that local calls are better transmitted and less degraded than foreign calls (i.e. acoustic adaptation hypothesis). Overall, the advertisement calls varied greatly along the distribution of P. thaul in Chile, and it was possible to discriminate localities grouped into northern, central and southern stocks. Propagation distance affected signal amplitude and spectral degradation in all localities, but temporal degradation was only affected by propagation distance in one out of seven localities. Call origin affected signal amplitude in five out of seven localities and affected spectral and temporal degradation in six out of seven localities. In addition, in northern localities, local calls degraded more than foreign calls, and in southern localities the opposite was observed. The lack of a strict optimal relationship between signal characteristics and environment indicates partial concordance with the acoustic adaptation hypothesis. Inter-population differences in selectivity for call patterns may compensate for such environmental constraints on acoustic communication.