bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spatio-temporal analysis of coding and long noncoding transcripts during maize endosperm development
Authors: Kim Eun-Deok , Xiong Yuqing , Pyo Youngjae , Kim Dong-Hwan , Kang Byung-Ho , Sung Sibum 
Published: June 2017

AbstractThe maize endosperm consists of three major compartmentalized cell types: the starchy endosperm (SE), the basal endosperm transfer cell layer (BETL), and the aleurone cell layer (AL). Differential genetic programs are activated in each cell type to construct functionally and structurally distinct cells. To compare gene expression patterns involved in maize endosperm cell differentiation, we isolated transcripts from cryo-dissected endosperm specimens enriched with BETL, AL, or SE at 8, 12, and 16 days after pollination (DAP). We performed transcriptome profiling of coding and long noncoding transcripts in the three cell types during differentiation and identified clusters of the transcripts exhibiting spatio-temporal specificities. Our analysis uncovered that the BETL at 12 DAP undergoes the most dynamic transcriptional regulation for both coding and long noncoding transcripts. In addition, our transcriptome analysis revealed spatio-temporal regulatory networks of transcription factors, imprinted genes, and loci marked with histone H3 trimethylated at lysine 27. Our study suggests that various regulatory mechanisms contribute to the genetic networks specific to the functions and structures of the cell types of the endosperm.
Phylogenetic analysis of F-bZIP transcription factors indicates conservation of the zinc deficiency response across land plants
Authors: Castro Pedro Humberto , Lilay Grmay H. , Muñoz-Mérida Antonio , Schjoerring Jan K. , Azevedo Herlânder , Assunção Ana G. L. 
Published: June 2017

AbstractBasic leucine zipper (bZIP) transcription factors control important developmental and physiological processes in plants. InArabidopsis thaliana, the three gene F-bZIP subfamily has been associated with zinc deficiency and salt stress response. Benefiting from the present abundance of plant genomic data, we performed an evolutionary and structural characterization of plant F-bZIPs. We observed divergence during seed plant evolution, into two groups and inferred different selective pressures for each. Group 1 contains AtbZIP19 and AtbZIP23 and appears more conserved, whereas Group 2, containing AtbZIP24, is more prone to gene loss and expansion events. Transcriptomic and experimental data reinforced AtbZIP19/23 as pivotal regulators of the zinc deficiency response, mostly via the activation of genes from the ZIP metal transporter family, and revealed that they are the main regulatory switch ofAtZIP4. A survey ofAtZIP4orthologs promoters across different plant taxa revealed an enrichment of theZinc Deficiency Response Element(ZDRE) to which both AtbZIP19/23 bind. Overall, our results indicate that while the AtbZIP24 function in the regulation of the salt stress response may be the result of neo-functionalization, the AtbZIP19/23 function in the regulation of the zinc deficiency response may be conserved in land plants (Embryophytes).
Computational method allowing Hydrogen-Deuterium Exchange Mass Spectrometry at single amide Resolution
Authors: Gessner Chris , Steinchen Wieland , Bédard Sabrina , J. Skinner John , Woods Virgil L. , Walsh Thomas J. , Bange Gert , Pantazatos Dionysios P. 
Published: June 2017

AbstractHydrogen-deuterium exchange (HDX) coupled with mass spectrometry (HDXMS) is a rapid and effective method for localizing and determining protein stability and dynamics. Localization is routinely limited to a peptide resolution of 5 to 20 amino acid residues. HDXMS data can contain information beyond that needed for defining protein stability at single amide resolution. Here we present a method for extracting this information from an HDX dataset to generate a HDXMS protein stability fingerprint. High resolution (HR)-HDXMS was applied to the analysis of a model protein of a spectrin tandem repeat that exemplified an intuitive stability profile based on the linkage of two triple helical repeats connected by a helical linker. The fingerprint recapitulated expected stability maximums and minimums with interesting structural features that corroborate proposed mechanisms of spectrin flexibility and elasticity. HR-HDXMS provides the unprecedented ability to accurately assess protein stability at the resolution of a single amino acid. The determination of HDX stability fingerprints may be broadly applicable in many applications for understanding protein structure and function as well as protein ligand interactions.
RETRACTED ARTICLE: New molecular tools in Neospora caninum for studying apicomplexan parasite proteins
Authors: Mota Caroline M. , Chen Allan L. , Wang Kevin , Nadipuram Santhosh , Vashisht Ajay A. , Wohlschlegel James A. , Mineo Tiago W. P. , Bradley Peter J. 
Published: June 2017

AbstractThe development of molecular genetics has greatly enhanced the study of the biology and pathology associated with parasites of the phylum Apicomplexa. We have established a system specifically designed for Neospora caninum, and used this system as a heterologous platform for the expression of foreign genes. Plasmid constructs containing fluorescent proteins or targeted genes of Toxoplasma gondii, driven by N. caninum promoters, have yielded robust expression and correct trafficking of target gene products as assessed by immunofluorescence assays and Western blot analyses. Using this approach, we here demonstrated that N. caninum expressing T. gondii’s GRA15 and ROP16 kinase are biologically active and induced immunological phenotypes consistent with T. gondii strains. N. caninum expressing TgGRA15 differentially disturbed the NF-κB pathway, inducing an increased IL-12 production. On the other hand, N. caninum expressing TgROP16 induced host STAT3 phosphorylation and consequent reduction of IL-12 synthesis. These results indicate that heterologous gene expression in N. caninum is a useful tool for the study of specific gene functions and may allow the identification of antigenic targets responsible for the phenotypic differences observed between these two closely related apicomplexan parasites. Additionally, these observations may prove to be useful for the development of vaccine protocols to control toxoplasmosis and/or neosporosis.
Role of methionine adenosyltransferase 2A in bovine preimplantation development and its associated genomic regions
Authors: Ikeda Shuntaro , Kawahara-Miki Ryouka , Iwata Hisataka , Sugimoto Miki , Kume Shinichi 
Published: June 2017

AbstractMethionine adenosyltransferase (MAT) is involved in folate-mediated one-carbon metabolism, which is essential for preimplantation embryos in terms of both short-term periconceptional development and long-term phenotypic programming beyond the periconceptional period. Here, our immunofluorescence analysis of bovine oocytes and preimplantation embryos revealed the consistent expression of MAT2A (the catalytic subunit of the ubiquitously expressed-type of MAT isozyme) during this period. Addition of the MAT2A inhibitor FIDAS to the culture media of bovine preimplantation embryos reduced their blastocyst development, revealing the particular importance of MAT2A in successful blastocyst development. Exploration of MAT2A-associated genomic regions in bovine blastocysts using chromatin immunoprecipitation and sequencing (ChIP-seq) identified candidate MAT2A-associated genes implicated not only in short-term periconceptional embryo development, but also in long-term phenotypic programming during this period in terms of growth, metabolism, and immune functions. These results suggest the critical involvement of MAT2A in the periconceptional period in life-long programming of health and disease as well as successful preimplantation development.
Nuclear accumulation of symplekin promotes cellular proliferation and dedifferentiation in an ERK1/2-dependent manner
Authors: Zhang Chen , Mao Hai-Lei , Cao Yi 
Published: June 2017

AbstractSymplekin is a multifunctional protein that localizes to both tight junctions and the nucleus in polarized epithelial cells, with confirmed roles in mRNA maturation, transcriptional modulation and tight-junction assembly. However, the mechanisms governing its subcellular distribution and related functions remain unclear. In this study, we found that symplekin primarily localizes to the nuclei of cultured dedifferentiated colorectal cancer cells, and nuclear symplekin showed higher phosphorylation and binding affinity with YBX3 than its membrane fraction. Moreover, the accumulation of nuclear symplekin promoted cell proliferation and dedifferentiation as well as β-catenin transactivation in vitro. Nuclear symplekin acts as a transcriptional co-activator for the expression of many cell cycle-related genes. Furthermore, extracellular signal-regulated kinase (ERK) phosphorylated symplekin at T1257 to facilitate its nuclear accumulation upon epidermal growth factor (EGF) stimulation. Meanwhile, reduction of total symplekin also induced certain epithelial-mesenchymal transition features in HT-29 cells. Taken together, our results confirm the coordinated roles of symplekin in cell junctions and gene transcription, which are related to its subcellular localization. The significance of nuclear symplekin in tumorigenesis is also highlighted, and ERK-dependent phosphorylation represents a mechanism for its subcellular sorting.
Integrated optical modulator manipulating the polarization and rotation handedness of Orbital Angular Momentum states
Authors: Mousavi S. Faezeh , Nouroozi Rahman , Vallone Giuseppe , Villoresi Paolo 
Published: June 2017

AbstractRecent studies demonstrated that the optical channels encoded by Orbital Angular Momentum (OAM) are capable candidates for improving the next generation of communication systems. OAM states can enhance the capacity and security of high-dimensional communication channels in both classical and quantum regimes based on optical fibre and free space. Hence, fast and precise control of the beams encoded by OAM can provide their commercial applications in the compatible communication networks. Integrated optical devices are good miniaturized options to perform this issue. This paper proposes a numerically verified integrated high-frequency electro-optical modulator for manipulation of the guided modes encoded in both OAM and polarization states. The proposed modulator is designed as an electro-optically active Lithium Niobate (LN) core photonic wire with silica as its cladding in a LN on Insulator (LNOI) configuration. It consists of two successive parts; a phase shifter to reverse the rotation handedness of the input OAM state and a polarization converter to change the horizontally polarized OAM state to the vertically polarized one. It is shown that all four possible output polarization-OAM encoded states can be achieved with only 6 V and 7 V applied voltages to the electrodes in the two parts of the modulator.
Pyroptosis, superinfection, and the maintenance of the latent reservoir in HIV-1 infection
Authors: Wodarz Dominik , Levy David N. 
Published: June 2017

AbstractA long-lived reservoir of latently infected T cells prevents antiretroviral therapy from eliminating HIV-1 infection. Furthering our understanding of the dynamics of latency generation and maintenance is therefore vital to improve treatment outcome. Using mathematical models and experiments, we suggest that the death of latently infected cells brought about by pyroptosis, or to a lesser extent by superinfection, might be key mechanisms to account for the size and composition of the latent reservoir. Pyroptosis is a form of cell death that occurs in a resting (and thus latently infected) T cell when a productively infected cell attempts cell-to-cell transmission of virus. Superinfection of latently infected cells by productive virus could similarly remove those cells through active virus replication and resulting cytopathicity. The mathematical models presented can explain a number of previously published clinical observations including latent reservoir size and the relationships to viral load in acute HIV infection, measurements of the latent reservoir in chronic infection, and the replacement of wild-type virus by CTL escape mutants within the latent reservoir. Basic virus dynamics models of latency that do not take into account pyroptosis, superinfection, or other potential complexities cannot account for the data.
Structure-Guided Design of C4-alkyl-1,4-dihydro-2H-pyrimido[4,5-d][1,3]oxazin-2-ones as Potent and Mutant-Selective Epidermal Growth Factor Receptor (EGFR) L858R/T790M Inhibitors
Authors: Hao Yongjia , Lyu Jiankun , Qu Rong , Sun Deheng , Zhao Zhenjiang , Chen Zhuo , Ding Jian , Xie Hua , Xu Yufang , Li Honglin 
Published: June 2017

AbstractEpidermal growth factor receptor (EGFR) T790M acquired drug-resistance mutation has become a major clinical challenge for the therapy of non-small cell lung cancer. Here, we applied a structure-guided approach on the basis of the previous reported EGFR inhibitor (compound 9), and designed a series of C4-alkyl-1,4-dihydro-2H-pyrimido[4,5-d][1,3]oxazin-2-one derivatives as novel mutant-selective EGFR inhibitors. Finally, the most representative compound 20a was identified, which showed high selectivity at both enzymatic and cellular levels against EGFRL858R/T790M (H1975 cell lines) over EGFRWT (A431 cell lines). The representative compound 20a also showed promising antitumor efficiency in the in vivo antitumor efficacy study of H1975 xenograft mouse model driven by EGFRL858R/T790M. These results provide a new scaffold for the treatment of dual-mutant-driven non-small cell lung cancer.
IFN-λ4 potently blocks IFN-α signalling by ISG15 and USP18 in hepatitis C virus infection
Authors: Sung Pil Soo , Hong Seon-Hui , Chung Jae-Hee , Kim Sojeong , Park Su-Hyung , Kim Ho Min , Yoon Seung Kew , Shin Eui-Cheol 
Published: June 2017

AbstractGenetic polymorphisms in IFNL4 have been shown to predict responses to IFN-α-based therapy in hepatitis C virus (HCV)-infected patients. The IFNL4-ΔG genotype, which encodes functional IFN-λ4 protein, is associated with a poor treatment response. In the present study, we investigated the induction and biological effects of IFN-λ4 in HCV-infected hepatocytes and their association with responsiveness to IFN-α. We also studied the effects of direct-acting antiviral (DAA) treatment on IFN-λ4 expression and IFN-α responsiveness. HCV infection induced IFN-λ4 expression at mRNA and protein levels in primary human hepatocytes (PHHs). In hepatoma cells, IFNL4 gene transfection or recombinant IFN-λ4 protein treatment robustly increased the protein levels of ISG15 and USP18 in an IFNLR1-dependent manner and potently blocked IFN-α signalling. The ISG15/USP18-mediated IFN-α unresponsiveness was demonstrated by transfection of siRNAs targeting ISG15 and/or USP18. This potent IFN-λ4 effect was related to prolonged ISG expression after IFNL4 gene transfection. DAA treatment of HCV-infected PHHs reduced the expression of IFN-λs, including IFN-λ4, and restored IFN-α responsiveness. These results demonstrate that virus-induced IFN-λ4 potently blocks IFN-α signalling by inducing high protein levels of ISG15 and USP18. Moreover, the data clearly demonstrate that DAA therapy restores IFN-α responsiveness in HCV-infected cells.
Down-regulation of KCa2.3 channels causes erectile dysfunction in mice
Authors: Comerma-Steffensen Simon , Kun Attila , Hedegaard Elise R. , Mogensen Susie , Aalkjaer Christian , Köhler Ralf , Mønster Christensen Birgitte , Simonsen Ulf 
Published: June 2017

AbstractModulation of endothelial calcium-activated K+ channels has been proposed as an approach to restore arterial endothelial cell function in disease. We hypothesized that small-conductance calcium-activated K+ channels (KCa2.3 or SK3) contributes to erectile function. The research was performed in transgenic mice with overexpression (KCa2.3
T/T(−Dox)) or down-regulation (KCa2.3
T/T(+Dox)) of the KCa2.3 channels and wild-type C57BL/6-mice (WT). QPCR revealed that KCa2.3 and KCa1.1 channels were the most abundant in mouse corpus cavernosum. KCa2.3 channels were found by immunoreactivity and electron microscopy in the apical-lateral membrane of endothelial cells in the corpus cavernosum. Norepinephrine contraction was enhanced in the corpus cavernosum of KCa2.3
T/T(+Dox)versus KCa2.3
T/T(−Dox) mice, while acetylcholine relaxation was only reduced at 0.3 µM and relaxations in response to the nitric oxide donor sodium nitroprusside were unaltered. An opener of KCa2 channels, NS309 induced concentration-dependent relaxations of corpus cavernosum. Mean arterial pressure was lower in KCa2.3
T/T(−Dox) mice compared with WT and KCa2.3
T/T(+Dox) mice. In anesthetized mice, cavernous nerve stimulation augmented in frequency/voltage dependent manner erectile function being lower in KCa2.3
T/T(+Dox) mice at low frequencies. Our findings suggest that down-regulation of KCa2.3 channels contributes to erectile dysfunction, and that pharmacological activation of KCa2.3 channels may have the potential to restore erectile function.
Concurrent talking in immersive virtual reality: on the dominance of visual speech cues
Authors: Gonzalez-Franco Mar , Maselli Antonella , Florencio Dinei , Smolyanskiy Nikolai , Zhang Zhengyou 
Published: June 2017

AbstractHumans are good at selectively listening to specific target conversations, even in the presence of multiple concurrent speakers. In our research, we study how auditory-visual cues modulate this selective listening. We do so by using immersive Virtual Reality technologies with spatialized audio. Exposing 32 participants to an Information Masking Task with concurrent speakers, we find significantly more errors in the decision-making processes triggered by asynchronous audiovisual speech cues. More precisely, the results show that lips on the Target speaker matched to a secondary (Mask) speaker’s audio severely increase the participants’ comprehension error rates. In a control experiment (n = 20), we further explore the influences of the visual modality over auditory selective attention. The results show a dominance of visual-speech cues, which effectively turn the Mask into the Target and vice-versa. These results reveal a disruption of selective attention that is triggered by bottom-up multisensory integration. The findings are framed in the sensory perception and cognitive neuroscience theories. The VR setup is validated by replicating previous results in this literature in a supplementary experiment.
Towards affordable biomarkers of frontotemporal dementia: A classification study via network’s information sharing
Authors: Dottori Martin , Sedeño Lucas , Martorell Caro Miguel , Alifano Florencia , Hesse Eugenia , Mikulan Ezequiel , García Adolfo M. , Ruiz-Tagle Amparo , Lillo Patricia , Slachevsky Andrea , Serrano Cecilia , Fraiman Daniel , Ibanez Agustin 
Published: June 2017

AbstractDeveloping effective and affordable biomarkers for dementias is critical given the difficulty to achieve early diagnosis. In this sense, electroencephalographic (EEG) methods offer promising alternatives due to their low cost, portability, and growing robustness. Here, we relied on EEG signals and a novel information-sharing method to study resting-state connectivity in patients with behavioral variant frontotemporal dementia (bvFTD) and controls. To evaluate the specificity of our results, we also tested Alzheimer’s disease (AD) patients. The classification power of the ensuing connectivity patterns was evaluated through a supervised classification algorithm (support vector machine). In addition, we compared the classification power yielded by (i) functional connectivity, (ii) relevant neuropsychological tests, and (iii) a combination of both. BvFTD patients exhibited a specific pattern of hypoconnectivity in mid-range frontotemporal links, which showed no alterations in AD patients. These functional connectivity alterations in bvFTD were replicated with a low-density EEG setting (20 electrodes). Moreover, while neuropsychological tests yielded acceptable discrimination between bvFTD and controls, the addition of connectivity results improved classification power. Finally, classification between bvFTD and AD patients was better when based on connectivity than on neuropsychological measures. Taken together, such findings underscore the relevance of EEG measures as potential biomarker signatures for clinical settings.
Single phase 3D phononic band gap material
Authors: Warmuth Franziska , Wormser Maximilian , Körner Carolin 
Published: June 2017

AbstractPhononic band gap materials are capable of prohibiting the propagation of mechanical waves in certain frequency ranges. Band gaps are produced by combining different phases with different properties within one material. In this paper, we present a novel cellular material consisting of only one phase with a phononic band gap. Different phases are modelled by lattice structure design based on eigenmode analysis. Test samples are built from a titanium alloy using selective electron beam melting. For the first time, the predicted phononic band gaps via FEM simulation are experimentally verified. In addition, it is shown how the position and extension of the band gaps can be tuned by utilizing knowledge-based design.
Predicting the Reliability of Drug-target Interaction Predictions with Maximum Coverage of Target Space
Authors: Peón Antonio , Naulaerts Stefan , Ballester Pedro J. 
Published: June 2017

AbstractMany computational methods to predict the macromolecular targets of small organic molecules have been presented to date. Despite progress, target prediction methods still have important limitations. For example, the most accurate methods implicitly restrict their predictions to a relatively small number of targets, are not systematically validated on drugs (whose targets are harder to predict than those of non-drug molecules) and often lack a reliability score associated with each predicted target. Here we present a systematic validation of ligand-centric target prediction methods on a set of clinical drugs. These methods exploit a knowledge-base covering 887,435 known ligand-target associations between 504,755 molecules and 4,167 targets. Based on this dataset, we provide a new estimate of the polypharmacology of drugs, which on average have 11.5 targets below IC50 10 µM. The average performance achieved across clinical drugs is remarkable (0.348 precision and 0.423 recall, with large drug-dependent variability), especially given the unusually large coverage of the target space. Furthermore, we show how a sparse ligand-target bioactivity matrix to retrospectively validate target prediction methods could underestimate prospective performance. Lastly, we present and validate a first-in-kind score capable of accurately predicting the reliability of target predictions.