bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficient Suppression of Hepatitis C Virus Replication by Combination Treatment with miR-122 Antagonism and Direct-acting Antivirals in Cell Culture Systems
Authors: Liu Fanwei , Shimakami Tetsuro , Murai Kazuhisa , Shirasaki Takayoshi , Funaki Masaya , Honda Masao , Murakami Seishi , Yi Minkyung , Tang Hong , Kaneko Shuichi 
Published: August 2016

AbstractDirect-acting antivirals (DAAs) against Hepatitis C virus (HCV) show effective antiviral activity with few side effects. However, the selection of DAA-resistance mutants is a growing problem that needs to be resolved. In contrast, miR-122 antagonism shows extensive antiviral effects among all HCV genotypes and a high barrier to drug resistance. In the present study, we evaluated three DAAs (simeprevir, daclatasvir and sofosbuvir) in combination with anti-miR-122 treatment against HCV genotype 1a in cell cultures. We found that combination treatments with anti-miR-122 and a DAA had additive or synergistic antiviral effects. The EC50 values of simeprevir in simeprevir-resistant mutants were significantly decreased by combining simeprevir with anti-miR-122. A similar reduction in EC50 in daclatasvir-resistant mutants was achieved by combining daclatasvir with anti-miR-122. Combination treatment in HCV-replicating cells with DAA and anti-miR-122 sharply reduced HCV RNA amounts. Conversely, DAA single treatment with simeprevir or daclatasvir reduced HCV RNA levels initially, but the levels later rebounded. DAA-resistant mutants were less frequently observed in combination treatments than in DAA single treatments. In summary, the addition of miR-122 antagonism to DAA single treatments had additive or synergistic antiviral effects and helped to efficiently suppress HCV replication and the emergence of DAA-resistant mutants.
Fiberless multicolor neural optoelectrode for in vivo circuit analysis
Authors: Kampasi Komal , Stark Eran , Seymour John , Na Kyounghwan , Winful Herbert G. , Buzsáki György , Wise Kensall D. , Yoon Euisik 
Published: August 2016

AbstractMaximizing the potential of optogenetic approaches in deep brain structures of intact animals requires optical manipulation of neurons at high spatial and temporal resolutions, while simultaneously recording electrical data from those neurons. Here, we present the first fiber-less optoelectrode with a monolithically integrated optical waveguide mixer that can deliver multicolor light at a common waveguide port to achieve multicolor modulation of the same neuronal population in vivo. We demonstrate successful device implementation by achieving efficient coupling between a side-emitting injection laser diode (ILD) and a dielectric optical waveguide mixer via a gradient-index (GRIN) lens. The use of GRIN lenses attains several design features, including high optical coupling and thermal isolation between ILDs and waveguides. We validated the packaged devices in the intact brain of anesthetized mice co-expressing Channelrhodopsin-2 and Archaerhodopsin in pyramidal cells in the hippocampal CA1 region, achieving high quality recording, activation and silencing of the exact same neurons in a given local region. This fully-integrated approach demonstrates the spatial precision and scalability needed to enable independent activation and silencing of the same or different groups of neurons in dense brain regions while simultaneously recording from them, thus considerably advancing the capabilities of currently available optogenetic toolsets.
Genome-wide association study of aggressive behaviour in chicken
Authors: Li Zhenhui , Zheng Ming , Abdalla Bahareldin Ali , Zhang Zhe , Xu Zhenqiang , Ye Qiao , Xu Haiping , Luo Wei , Nie Qinghua , Zhang Xiquan 
Published: August 2016

AbstractIn the poultry industry, aggressive behaviour is a large animal welfare issue all over the world. To date, little is known about the underlying genetics of the aggressive behaviour. Here, we performed a genome-wide association study (GWAS) to explore the genetic mechanism associated with aggressive behaviour in chickens. The GWAS results showed that a total of 33 SNPs were associated with aggressive behaviour traits (P < 4.6E-6). rs312463697 on chromosome 4 was significantly associated with aggression (P = 2.10905E-07) and it was in the intron region of the sortilin-related VPS10 domain containing receptor 2 (SORCS2) gene. In addition, biological function analysis of the nearest 26 genes around the significant SNPs was performed with Ingenuity Pathway Analysis. An interaction network contained 17 genes was obtained and SORCS2 was involved in this network, interacted with nerve growth factor (NGF), nerve growth factor receptor (NGFR), dopa decarboxylase (L-dopa) and dopamine. After knockdown of SORCS2, the mRNA levels of NGF, L-dopa and dopamine receptor genes DRD1, DRD2, DRD3 and DRD4 were significantly decreased (P < 0.05). In summary, our data indicated that SORCS2 might play an important role in chicken aggressive behaviour through the regulation of dopaminergic pathways and NGF.
1H NMR metabolomic study of auxotrophic starvation in yeast using Multivariate Curve Resolution-Alternating Least Squares for Pathway Analysis
Authors: Puig-Castellví Francesc , Alfonso Ignacio , Piña Benjamin , Tauler Romà 
Published: August 2016

AbstractDisruption of specific metabolic pathways constitutes the mode of action of many known toxicants and it is responsible for the adverse phenotypes associated to human genetic defects. Conversely, many industrial applications rely on metabolic alterations of diverse microorganisms, whereas many therapeutic drugs aim to selectively disrupt pathogens’ metabolism. In this work we analyzed metabolic changes induced by auxotrophic starvation conditions in yeast in a non-targeted approach, using one-dimensional proton Nuclear Magnetic Resonance spectroscopy (1H NMR) and chemometric analyses. Analysis of the raw spectral datasets showed specific changes linked to the different stages during unrestricted yeast growth, as well as specific changes linked to each of the four tested starvation conditions (L-methionine, L-histidine, L-leucine and uracil). Analysis of changes in concentrations of more than 40 metabolites by Multivariate Curve Resolution – Alternating Least Squares (MCR-ALS) showed the normal progression of key metabolites during lag, exponential and stationary unrestricted growth phases, while reflecting the metabolic blockage induced by the starvation conditions. In this case, different metabolic intermediates accumulated over time, allowing identification of the different metabolic pathways specifically affected by each gene disruption. This synergy between NMR metabolomics and molecular biology may have clear implications for both genetic diagnostics and drug development.
ZnCr2S4: Highly effective photocatalyst converting nitrate into N2 without over-reduction under both UV and pure visible light
Authors: Yue Mufei , Wang Rong , Cheng Nana , Cong Rihong , Gao Wenliang , Yang Tao 
Published: August 2016

AbstractWe propose several superiorities of applying some particular metal sulfides to the photocatalytic nitrate reduction in aqueous solution, including the high density of photogenerated excitons, high N2 selectivity (without over-reduction to ammonia). Indeed, ZnCr2S4 behaved as a highly efficient photocatalyst and with the assistance of 1 wt% cocatalysts (RuOx, Ag, Au, Pd, or Pt), the efficiency was greatly improved. The simultaneous loading of Pt and Pd led to a synergistic effect. It offered the highest nitrate conversion rate of ~45 mg N/h together with the N2 selectivity of ~89%. Such a high activity remained steady after 5 cycles. The optimal apparent quantum yield at 380 nm was 15.46%. More importantly, with the assistance of the surface plasma resonance effect of Au, the visible light activity achieved 1.352 mg N/h under full arc Xe-lamp and 0.452 mg N/h under pure visible light (λ > 400 nm). Comparing to the previous achievements in photocatalytic nitrate removal, our work on ZnCr2S4 eliminates the over-reduction problem and possesses an extremely high and steady activity under UV-light, as well as a decent conversion rate under pure visible light.
Dynamics Correlation Network for Allosteric Switching of PreQ1 Riboswitch
Authors: Wang Wei , Jiang Cheng , Zhang Jinmai , Ye Wei , Luo Ray , Chen Hai-Feng 
Published: August 2016

AbstractRiboswitches are a class of metabolism control elements mostly found in bacteria. Due to their fundamental importance in bacteria gene regulation, riboswitches have been proposed as antibacterial drug targets. Prequeuosine (preQ1) is the last free precursor in the biosynthetic pathway of queuosine that is crucial for translation efficiency and fidelity. However, the regulation mechanism for the preQ1riboswitch remains unclear. Here we constructed fluctuation correlation network based on all-atom molecular dynamics simulations to reveal the regulation mechanism. The results suggest that the correlation network in the bound riboswitch is distinctly different from that in the apo riboswitch. The community network indicates that the information freely transfers from the binding site of preQ1to the expression platform of the P3 helix in the bound riboswitch and the P3 helix is a bottleneck in the apo riboswitch. Thus, a hypothesis of “preQ1-binding induced allosteric switching” is proposed to link riboswitch and translation regulation. The community networks of mutants support this hypothesis. Finally, a possible allosteric pathway of A50-A51-A52-U10-A11-G12-G56 was also identified based on the shortest path algorithm and confirmed by mutations and network perturbation. The novel fluctuation network analysis method can be used as a general strategy in studies of riboswitch structure-function relationship.
Synaptic Basis for the Generation of Response Variation in Auditory Cortex
Authors: Tao Can , Zhang Guangwei , Zhou Chang , Wang Lijuan , Yan Sumei , Zhang Li I. , Zhou Yi , Xiong Ying 
Published: August 2016

AbstractCortical neurons can exhibit significant variation in their responses to the same sensory stimuli, as reflected by the reliability and temporal precision of spikes. However the synaptic mechanism underlying response variation still remains unclear. Here, in vivo whole-cell patch-clamp recording of excitatory neurons revealed variation in the amplitudes as well as the temporal profiles of excitatory and inhibitory synaptic inputs evoked by the same sound stimuli in layer 4 of the rat primary auditory cortex. Synaptic inputs were reliably induced by repetitive stimulation, although with large variation in amplitude. The variation in the amplitude of excitation was much higher than that of inhibition. In addition, the temporal jitter of the synaptic onset latency was much smaller than the jitter of spike response. We further demonstrated that the amplitude variation of excitatory inputs can largely account for the spike variation, while the jitter in spike timing can be primarily attributed to the temporal variation of excitatory inputs. Furthermore, the spike reliability of excitatory but not inhibitory neurons is dependent on tone frequency. Our results thus revealed an inherent cortical synaptic contribution for the generation of variation in the spike responses of auditory cortical neurons.
Advanced Mitigation Process (AMP) for Improving Laser Damage Threshold of Fused Silica Optics
Authors: Ye Xin , Huang Jin , Liu Hongjie , Geng Feng , Sun Laixi , Jiang Xiaodong , Wu Weidong , Qiao Liang , Zu Xiaotao , Zheng Wanguo 
Published: August 2016

AbstractThe laser damage precursors in subsurface of fused silica (e.g. photosensitive impurities, scratches and redeposited silica compounds) were mitigated by mineral acid leaching and HF etching with multi-frequency ultrasonic agitation, respectively. The comparison of scratches morphology after static etching and high-frequency ultrasonic agitation etching was devoted in our case. And comparison of laser induce damage resistance of scratched and non-scratched fused silica surfaces after HF etching with high-frequency ultrasonic agitation were also investigated in this study. The global laser induce damage resistance was increased significantly after the laser damage precursors were mitigated in this case. The redeposition of reaction produce was avoided by involving multi-frequency ultrasonic and chemical leaching process. These methods made the increase of laser damage threshold more stable. In addition, there is no scratch related damage initiations found on the samples which were treated by Advanced Mitigation Process.
A CRISPR-Cas9 sex-ratio distortion system for genetic control
Authors: Galizi Roberto , Hammond Andrew , Kyrou Kyros , Taxiarchi Chrysanthi , Bernardini Federica , O’Loughlin Samantha M. , Papathanos Philippos-Aris , Nolan Tony , Windbichler Nikolai , Crisanti Andrea 
Published: August 2016

AbstractGenetic control aims to reduce the ability of insect pest populations to cause harm via the release of modified insects. One strategy is to bias the reproductive sex ratio towards males so that a population decreases in size or is eliminated altogether due to a lack of females. We have shown previously that sex ratio distortion can be generated synthetically in the main human malaria vector Anopheles gambiae, by selectively destroying the X-chromosome during spermatogenesis, through the activity of a naturally-occurring endonuclease that targets a repetitive rDNA sequence highly-conserved in a wide range of organisms. Here we describe a CRISPR-Cas9 sex distortion system that targets ribosomal sequences restricted to the member species of the Anopheles gambiae complex. Expression of Cas9 during spermatogenesis resulted in RNA-guided shredding of the X-chromosome during male meiosis and produced extreme male bias among progeny in the absence of any significant reduction in fertility. The flexibility of CRISPR-Cas9 combined with the availability of genomic data for a range of insects renders this strategy broadly applicable for the species-specific control of any pest or vector species with an XY sex-determination system by targeting sequences exclusive to the female sex chromosome.
Divergent Annexin A1 expression in periphery and gut is associated with systemic immune activation and impaired gut immune response during SIV infection
Authors: Sena Angela A. S. , Glavan Tiffany , Jiang Guochun , Sankaran-Walters Sumathi , Grishina Irina , Dandekar Satya , Goulart Luiz R. 
Published: August 2016

AbstractHIV-1 disease progression is paradoxically characterized by systemic chronic immune activation and gut mucosal immune dysfunction, which is not fully defined. Annexin A1 (ANXA1), an inflammation modulator, is a potential link between systemic inflammation and gut immune dysfunction during the simian immunodeficiency virus (SIV) infection. Gene expression of ANXA1 and cytokines were assessed in therapy-naïve rhesus macaques during early and chronic stages of SIV infection and compared with SIV-negative controls. ANXA1 expression was suppressed in the gut but systemically increased during early infection. Conversely, ANXA1 expression increased in both compartments during chronic infection. ANXA1 expression in peripheral blood was positively correlated with HLA-DR+CD4+ and CD8+ T-cell frequencies and negatively associated with the expression of pro-inflammatory cytokines and CCR5. In contrast, the gut mucosa presented an anergic cytokine profile in relation to ANXA1 expression. In vitro stimulations with ANXA1 peptide resulted in decreased inflammatory response in PBMC but increased activation of gut lymphocytes. Our findings suggest that ANXA1 signaling is dysfunctional in SIV infection and may contribute to chronic inflammation in periphery and with immune dysfunction in the gut mucosa. Thus, ANXA1 signaling may be a novel therapeutic target for the resolution of immune dysfunction in HIV infection.
An efficient method to estimate the optimum regularization parameter in RLDA
Authors: Bakir Daniyar , James Alex Pappachen , Zollanvari Amin 
Published: August 2016

Motivation: The biomarker discovery process in high-throughput genomic profiles has presented the statistical learning community with a challenging problem, namely learning when the number of variables is comparable or exceeding the sample size. In these settings, many classical techniques including linear discriminant analysis (LDA) falter. Poor performance of LDA is attributed to the ill-conditioned nature of sample covariance matrix when the dimension and sample size are comparable. To alleviate this problem, regularized LDA (RLDA) has been classically proposed in which the sample covariance matrix is replaced by its ridge estimate. However, the performance of RLDA depends heavily on the regularization parameter used in the ridge estimate of sample covariance matrix.
Results: We propose a range-search technique for efficient estimation of the optimum regularization parameter. Using an extensive set of simulations based on synthetic and gene expression microarray data, we demonstrate the robustness of the proposed technique to Gaussianity, an assumption used in developing the core estimator. We compare the performance of the technique in terms of accuracy and efficiency with classical techniques for estimating the regularization parameter. In terms of accuracy, the results indicate that the proposed method vastly improves on similar techniques that use classical plug-in estimator. In that respect, it is better or comparable to cross-validation-based search strategies while, depending on the sample size and dimensionality, being tens to hundreds of times faster to compute.
Availability and Implementation: The source code is available at https://github.com/danik0411/optimum-rlda
Contact: amin.zollanvari@nu.edu.kz
Supplementary information: Supplementary materials are available at Bioinformatics online.
Education policies and organizational structures in Argentinian secondary schools
Authors: Vicente María Eugenia 
Published: August 2016

Purpose
– The purpose of this paper is to review the link between public education policies and institutional practices in Argentina throughout history and today.

Design/methodology/approach
– The methodology used is in line with socio-educational management studies oriented to analyse educational practices qualitatively from an institutional perspective.

Findings
– The review allows a wider discussion about the characteristics of the traditional organizational structure in relation to the rules, order, purposes and homogeneity of educational institutions. Furthermore, the paper shows there are some experiences and practices developed nowadays in Argentinian secondary schools that constitute a guide for social inclusion.

Research limitations/implications
– Throughout Argentina’s education history, secondary school has supported its policies on a bureaucratic institutional structure rationally oriented to serving interests of a minority. Today, social inclusion policies and compulsory secondary schooling are presented as an opportunity to democratize the management of educational institutions.

Practical implications
– In the early 2000s, the education system in Argentina kept a traditional bureaucratic structure based on a selective education policy. In this regard, statistics are quite revealing as regards the degree of social exclusion in secondary school: only 11 per cent of the students that begin first grade, finish secondary school. In 2006, after the enactment of the compulsory secondary education law, educational management is faced with the challenge to renew its institutional practices in order to make inclusion feasible. In this sense, the paper shows that secondary schools are implementing certain management practices aimed at achieving greater social inclusion.

Originality/value
– The paper focuses on the notion that the characteristics of management practices are related to the social interests of education policies. In this sense, the educational management of Argentinian secondary schools is undergoing a process of transformation from traditional selective practices towards more inclusive practices.
Pricing for higher education institutions: a value-based approach
Authors: Mohd Amir Amizawati , Md Auzair Sofiah , MAELAH RUHANITA , Ahmad Azlina 
Published: August 2016

Purpose
– The purpose of this paper is to propose the concept of higher education institutions (HEIs) offering educational services based on value for money. The value is determined based on customers’ (i.e. students) expectations of the service and the costs in comparison to the competitors. Understanding the value and creating customer value are a means to attain competitive advantage and constitute the basis of price setting. Drawing upon this belief, as an initial step towards value-based pricing method, the possible value factors are suggested for calculating educational programme prices across HEIs.

Design/methodology/approach
– This is a conceptual paper introducing the value-based pricing approach in setting HEI tuition fees. Extending prior discussion on the demand for quality education and current financial challenges faced by HEIs, it introduces the concept pricing based upon customer perceived value (student/industry). Value-based pricing is deemed appropriate in view of the value of short tangible and intangible investment by both parties (students and HEIs) to differentiate in terms of setting the right price for the right university for the right student.

Findings
– The primary aim is to suggest the applicability of value-based pricing for HEIs, which is likely to be both relevant and fruitful for the sustainability of the sector. It represents a personal point of view; building upon a review of the literature, the paper extends the established knowledge one step further in terms of setting the right price for the right university, which is deemed worthy of further study and development.

Originality/value
– The paper will be of use to the management and policymakers in the education sector in searching for a contemporary pricing mechanism for higher education.
Principal empowering leadership and teacher innovative behavior: a moderated mediation model
Authors: Gkorezis Panagiotis 
Published: August 2016

Purpose– The purpose of this paper is to contribute to extant literature by linking principal empowering leadership to teachers’ innovative work behavior. By doing so, the author attempts to provide a more nuanced understanding of this relationship by examining a moderated mediation model which encompasses exploration as a mediator and role conflict as a moderator.Design/methodology/approach– Data were collected from 201 public teachers. In order to examine the present hypotheses bootstrapping analysis, Sobel test and SPSS macro were used.Findings– The results demonstrated that teacher exploration mediates the relationship between empowering leadership and innovative work behavior and, further, that this indirect effect is contingent on role conflict.Practical implications– Based on the present findings, in order to enhance innovation, schools need to promote both empowering leadership style and their teachers’ exploration. Moreover, principals should refrain from providing conflicting orders and expectations from their teachers because such conditions will eliminate the positive effect of their empowering behaviors on teachers’ exploration and innovative work behavior.Originality/value– This is the first study that develops and tests a moderated mediation model regarding the relationship between principal empowering leadership and teacher innovative behavior.