bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Dual-Specific Targeting Approach Based on the Simultaneous Recognition of Duplex and Quadruplex Motifs
Authors: Nguyen Thi Quynh Ngoc , Lim Kah Wai , Phan Anh Tuân 
Published: September 2017

AbstractSmall-molecule ligands targeting nucleic acids have been explored as potential therapeutic agents. Duplex groove-binding ligands have been shown to recognize DNA in a sequence-specific manner. On the other hand, quadruplex-binding ligands exhibit high selectivity between quadruplex and duplex, but show limited discrimination between different quadruplex structures. Here we propose a dual-specific approach through the simultaneous application of duplex- and quadruplex-binders. We demonstrated that a quadruplex-specific ligand and a duplex-specific ligand can simultaneously interact at two separate binding sites of a quadruplex-duplex hybrid harbouring both quadruplex and duplex structural elements. Such a dual-specific targeting strategy would combine the sequence specificity of duplex-binders and the strong binding affinity of quadruplex-binders, potentially allowing the specific targeting of unique quadruplex structures. Future research can be directed towards the development of conjugated compounds targeting specific genomic quadruplex-duplex sites, for which the linker would be highly context-dependent in terms of length and flexibility, as well as the attachment points onto both ligands.
Circulating Mycobacterium tuberculosis DosR latency antigen-specific, polyfunctional, regulatory IL10+ Th17 CD4 T-cells differentiate latent from active tuberculosis
Authors: Rakshit Srabanti , Adiga Vasista , Nayak Soumya , Sahoo Pravat Nalini , Sharma Prabhat Kumar , van Meijgaarden Krista E. , UK J. Anto Jesuraj , Dhar Chirag , Souza George D. , Finak Greg , De Rosa Stephen C. , Ottenhoff Tom H. M. , Vyakarnam Annapurna 
Published: September 2017

AbstractThe functional heterogeneity of T cell responses to diverse antigens expressed at different stages of Mycobacterium tuberculosis (Mtb) infection, in particular early secreted versus dormancy related latency antigens expressed later, that distinguish subjects with latent (LTBI), pulmonary (PTB) or extrapulmonary (EPTB) tuberculosis remains unclear. Here we show blood central memory CD4 T-cell responses specific to Mtb dormancy related (DosR) latency, but not classical immunodominant secretory antigens, to clearly differentiate LTBI from EPTB and PTB. The polyfunctionality score integrating up to 31 DosR-specific CD4 T-cell functional profiles was significantly higher in LTBI than EPTB or PTB subjects. Further analysis of 256 DosR-specific T-cell functional profiles identified regulatory IL10 + Th17 cells (IL10+IL17A+IL17F+IL22+) to be significantly enriched in LTBI; in contrast to pro-inflammatory Th17 cells (IFNγ+IL17A+/IL10−) in the blood and lung of EPTB and PTB subjects respectively. A blood polyfunctional, Mtb DosR latency antigen specific, regulatory, central memory response is therefore a novel functional component of T-cell immunity in latent TB and potential correlate of protection.
Energetics and mechanism of anion permeation across formate-nitrite transporters
Authors: Atkovska Kalina , Hub Jochen S. 
Published: September 2017

AbstractFormate-nitrite transporters (FNTs) facilitate the translocation of monovalent polyatomic anions, such as formate and nitrite, across biological membranes. FNTs are widely distributed among pathogenic bacteria and eukaryotic parasites, but they lack human homologues, making them attractive drug targets. The mechanisms and energetics involved in anion permeation across the FNTs have remained largely unclear. Both, channel and transporter mode of function have been proposed, with strong indication of proton coupling to the permeation process. We combine molecular dynamics simulations, quantum mechanical calculations, and pKa calculations, to compute the energetics of the complete permeation cycle of an FNT. We find that anions as such, are not able to traverse the FNT pore. Instead, anion binding into the pore is energetically coupled to protonation of a centrally located histidine. In turn, the histidine can protonate the permeating anion, thereby enabling its release. Such mechanism can accommodate the functional diversity among the FNTs, as it may facilitate both, export and import of substrates, with or without proton co-transport. The mechanism excludes proton leakage via the Grotthuss mechanism, and it rationalises the selectivity for weak acids.
Clinical and radiological diversity in genetically confirmed primary familial brain calcification
Authors: Koyama Shingo , Sato Hidenori , Kobayashi Ryota , Kawakatsu Shinobu , Kurimura Masayuki , Wada Manabu , Kawanami Toru , Kato Takeo 
Published: September 2017

AbstractPrimary familial brain calcification (PFBC) is a rare neuropsychiatric disorder with characteristic symmetrical brain calcifications. Patients with PFBC may have a variety of symptoms, although they also may be clinically asymptomatic. Parkinsonism is one of the most common movement disorders; however, the underlying mechanism remains unclear. This condition is typically transmitted in an autosomal dominant fashion. To date, mutations in SLC20A2, PDGFRB, PDGFB, and XPR1 have been reported to cause PFBC. The aim of the study was to identify the genetic cause of brain calcification in probands from three PFBC families and in 8 sporadic patients and to perform clinical and radiological assessments focusing on parkinsonism in mutation carriers. Three familial PFBC probands and their relatives and eight sporadic patients affected with brain calcifications were enrolled in this study. Whole-exome sequencing identified three novel mutations: c.269G > T, p.(Gly90Val) and c.516+1G > A in SLC20A2 in familial cases, and c.602-1G > T in PDGFB in a sporadic patient. The c.516+1G > A mutation resulted in exon 4 skipping in SLC20A2 (p.Val144Glyfs*85). Dopamine transporter single photon emission computed tomography using 123I-ioflupane and 123I-metaiodobenzylguanidine cardiac scintigraphy revealed pre-synaptic dopaminergic deficit and cardiac sympathetic nerve dysfunction in two SLC20A2-related PFBC patients with parkinsonism.
Identification of Genes Involved in Chemoreception in Plutella xyllostella by Antennal Transcriptome Analysis
Authors: Yang Shiyong , Cao Depan , Wang Guirong , Liu Yang 
Published: September 2017

AbstractPerception of environmental and habitat cues is of significance for insect survival and reproduction. Odor detection in insects is mediated by a number of proteins in antennae such as odorant receptors (ORs), ionotropic receptors (IRs), odorant binding proteins (OBPs), chemosensory proteins (CSPs), sensory neuron membrane proteins (SNMPs) and odorant degrading enzymes. In this study, we sequenced and assembled the adult male and female antennal transcriptomes of a destructive agricultural pest, the diamondback moth Plutella xyllostella. In these transcriptomes, we identified transcripts belonging to 6 chemoreception gene families related to ordor detection, including 54 ORs, 16 IRs, 7 gustatory receptors (GRs), 15 CSPs, 24 OBPs and 2 SNMPs. Semi-quantitative reverse transcription PCR analysis of expression patterns indicated that some of these ORs and IRs have clear sex-biased and tissue-specific expression patterns. Our results lay the foundation for future characterization of the functions of these P. xyllostella chemosensory receptors at the molecular level and development of novel semiochemicals for integrated control of this agricultural pest.
Mllt10 knockout mouse model reveals critical role of Af10-dependent H3K79 methylation in midfacial development
Authors: Ogoh Honami , Yamagata Kazutsune , Nakao Tomomi , Sandell Lisa L. , Yamamoto Ayaka , Yamashita Aiko , Tanga Naomi , Suzuki Mai , Abe Takaya , Kitabayashi Issay , Watanabe Toshio , Sakai Daisuke 
Published: September 2017

AbstractEpigenetic regulation is required to ensure the precise spatial and temporal pattern of gene expression that is necessary for embryonic development. Although the roles of some epigenetic modifications in embryonic development have been investigated in depth, the role of methylation at lysine 79 (H3K79me) is poorly understood. Dot1L, a unique methyltransferase for H3K79, forms complexes with distinct sets of co-factors. To further understand the role of H3K79me in embryogenesis, we generated a mouse knockout of Mllt10, the gene encoding Af10, one Dot1L complex co-factor. We find homozygous Mllt10 knockout mutants (Mllt10-KO) exhibit midline facial cleft. The midfacial defects of Mllt10-KO embryos correspond to hyperterolism and are associated with reduced proliferation of mesenchyme in developing nasal processes and adjacent tissue. We demonstrate that H3K79me level is significantly decreased in nasal processes of Mllt10-KO embryos. Importantly, we find that expression of AP2α, a gene critical for midfacial development, is directly regulated by Af10-dependent H3K79me, and expression AP2α is reduced specifically in nasal processes of Mllt10-KO embryos. Suppression of H3K79me completely mimicked the Mllt10-KO phenotype. Together these data are the first to demonstrate that Af10-dependent H3K79me is essential for development of nasal processes and adjacent tissues, and consequent midfacial formation.
Improvement of a fermentation process for the production of two PfAMA1-DiCo-based malaria vaccine candidates in Pichia pastoris
Authors: Kastilan Robin , Boes Alexander , Spiegel Holger , Voepel Nadja , Chudobová Ivana , Hellwig Stephan , Buyel Johannes Felix , Reimann Andreas , Fischer Rainer 
Published: September 2017

AbstractPichia pastorisis a simple and powerful expression platform that has the ability to produce a wide variety of recombinant proteins, ranging from simple peptides to complex membrane proteins. A well-established fermentation strategy is available comprising three main phases: a batch phase, followed by a glycerol fed-batch phase that increases cell density, and finally an induction phase for product expression using methanol as the inducer. We previously used this three-phase strategy at the 15-L scale to express three different AMA1-DiCo-based malaria vaccine candidates to develop a vaccine cocktail. For two candidates, we switched to a two-phase strategy lacking the intermediate glycerol fed-batch phase. The new strategy not only provided a more convenient process flow but also achieved 1.5-fold and 2.5-fold higher space-time yields for the two candidates, respectively, and simultaneously reduced the final cell mass by a factor of 1.3, thus simplifying solid–liquid separation. This strategy also reduced the quantity of host cell proteins that remained to be separated from the two vaccine candidates (by 34% and 13%, respectively), thus reducing the effort required in the subsequent purification steps. Taken together, our new fermentation strategy increased the overall fermentation performance for the production of two different AMA1-DiCo-based vaccine candidates.
Mediating Role of TRPV1 Ion Channels in the Co-exposure to PM2.5 and Formaldehyde of Balb/c Mice Asthma Model
Authors: Song Jing , Kang Jun , Lin Bencheng , Li Jinquan , Zhu Yuqing , Du Junting , Yang Xu , Xi Zhuge , Li Rui 
Published: September 2017

AbstractAsthma is a complex pulmonary inflammatory disease that can be promoted by air pollutants such as PM2.5 and formaldehyde (FA). However, existent experimental evidence principally focuses on the negative influence of a single air pollutant, neglecting the possible synergistic effect in biological responses to mixture of these pollutants, a more common situation in our daily life. In this study, allergic Balb/c mice were exposed to a mixture of PM2.5 and FA, and their toxicological effects and mechanisms were explored. It is demonstrated that the combined exposure to PM2.5 and FA can greatly aggravate allergic asthma in mice. When compared with exposure to PM2.5 or FA alone, the co-exposure showed a certain synergistic effect. Increased levels of ROS, inflammatory factors and total serum immunoglobulin E were concomitant with this deterioration. Furthermore, results suggested that co-exposure exacerbated the activation of TRPV1 signal pathways, with an enhancement in substance P and calcitonin gene-related peptide production, which contributed to inflammation in asthma by neurogenic inflammation. The study also proved that capsazepine treatment could reduce the levels of not only pro-inflammatory neuropeptides, but also oxidative stress. It is concluded that co-exposure to PM2.5 and FA exacerbated allergic asthma through oxidative stress and enhanced TRPV1 activation.
Simulation of early DNA damage after the irradiation of a fibroblast cell nucleus using Geant4-DNA
Authors: Meylan Sylvain , Incerti Sébastien , Karamitros Mathieu , Tang Nicolas , Bueno Marta , Clairand Isabelle , Villagrasa Carmen 
Published: September 2017

AbstractIn order to improve the understanding of the mechanisms involved in the generation of early DNA damage, a new calculation chain based on the Geant4-DNA toolkit was developed. This work presents for the first time the simulation of the physical, physicochemical and chemical stages of early radiation damage at the scale of an entire human genome (fibroblast, male) and using Geant4-DNA models. The DnaFabric software was extended to generate and export this nucleus model to a text file with a specific format that can be read by Geant4 user applications. This calculation chain was used to simulate the irradiation of the nucleus by primary protons of different energies (0,5; 0,7; 0,8; 1; 1,5; 2; 3; 4; 5; 10; 20 MeV) and the results, in terms of DNA double strand breaks, agree with experimental data found in the literature (pulsed field electrophoresis technique). These results show that the simulation is consistent and that its parameters are well balanced. Among the different parameters that can be adjusted, our results demonstrate that the criterion used to select direct strand break appears to have a very significant role on the final number of simulated double strand breaks.
Enhancing the Mechanical Toughness of Epoxy-Resin Composites Using Natural Silk Reinforcements
Authors: Yang Kang , Wu Sujun , Guan Juan , Shao Zhengzhong , Ritchie Robert O. 
Published: September 2017

AbstractStrong and tough epoxy composites are developed using a less-studied fibre reinforcement, that of natural silk. Two common but structurally distinct silks from the domestic B. mori/Bm and the wild A. pernyi/Ap silkworms are selected in fabric forms. We show that the toughening effects on silk-epoxy composites or SFRPs are dependent on the silk species and the volume fraction of silk. Both silks enhance the room-temperature tensile and flexural mechanical properties of the composite, whereas the more resilient Ap silk shows a more pronounced toughening effect and a lower critical reinforcement volume for the brittle-ductile transition. Specifically, our 60 vol.% Ap-SFRP displays a three-fold elevation in tensile and flexural strength, as compared to pure epoxy resin, with an order of magnitude higher breaking energy via a distinct, ductile failure mode. Importantly, the 60 vol.% Ap-SFRP remains ductile with 7% flexural elongation at lower temperatures (−50 °C). Under impact, these SFRPs show significantly improved energy absorption, and the 60 vol.% Ap-SFRP has an impact strength some eight times that of pure epoxy resin. The findings demonstrate both marked toughening and strengthening effects for epoxy composites from natural silk reinforcements, which presents opportunities for mechanically superior and “green” structural composites.
Calibrated Link Budget of a Silicon Photonics WDM Transceiver with SOA and Semiconductor Mode-Locked Laser
Authors: Moscoso-Mártir Alvaro , Müller Juliana , Islamova Elmira , Merget Florian , Witzens Jeremy 
Published: September 2017

AbstractBased on the single channel characterization of a Silicon Photonics (SiP) transceiver with Semiconductor Optical Amplifier (SOA) and semiconductor Mode-Locked Laser (MLL), we evaluate the optical power budget of a corresponding Wavelength Division Multiplexed (WDM) link in which penalties associated to multi-channel operation and the management of polarization diversity are introduced. In particular, channel cross-talk as well as Cross Gain Modulation (XGM) and Four Wave Mixing (FWM) inside the SOA are taken into account. Based on these link budget models, the technology is expected to support up to 12 multiplexed channels without channel pre-emphasis or equalization. Forward Error Correction (FEC) does not appear to be required at 14 Gbps if the SOA is maintained at 25 °C and MLL-to-SiP as well as SiP-to-SOA interface losses can be maintained below 3 dB. In semi-cooled operation with an SOA temperature below 55 °C, multi-channel operation is expected to be compatible with standard 802.3bj Reed-Solomon FEC at 14 Gbps provided interface losses are maintained below 4.5 dB. With these interface losses and some improvements to the Transmitter (Tx) and Receiver (Rx) electronics, 25 Gbps multi-channel operation is expected to be compatible with 7% overhead hard decision FEC.
THP-1-derived macrophages render lung epithelial cells hypo-responsive to Legionella pneumophila – a systems biology study
Authors: Schulz Christine , Lai Xin , Bertrams Wilhelm , Jung Anna Lena , Sittka-Stark Alexandra , Herkt Christina Elena , Janga Harshavadhan , Zscheppang Katja , Stielow Christina , Schulte Leon , Hippenstiel Stefan , Vera Julio , Schmeck Bernd 
Published: September 2017

AbstractImmune response in the lung has to protect the huge alveolar surface against pathogens while securing the delicate lung structure. Macrophages and alveolar epithelial cells constitute the first line of defense and together orchestrate the initial steps of host defense. In this study, we analysed the influence of macrophages on type II alveolar epithelial cells duringLegionella pneumophila-infection by a systems biology approach combining experimental work and mathematical modelling. We found thatL.pneumophila-infected THP-1-derived macrophages provoke a pro-inflammatory activation of neighboring lung epithelial cells, but in addition render them hypo-responsive to direct infection with the same pathogen. We generated a kinetic mathematical model of macrophage activation and identified a paracrine mechanism of macrophage-secreted IL-1β inducing a prolonged IRAK-1 degradation in lung epithelial cells. This intercellular crosstalk may help to avoid an overwhelming inflammatory response by preventing excessive local secretion of pro-inflammatory cytokines and thereby negatively regulating the recruitment of immune cells to the site of infection. This suggests an important but ambivalent immunomodulatory role of macrophages in lung infection.
Eu3+-activated La2MoO6-La2WO6 red-emitting phosphors with ultrabroad excitation band for white light-emitting diodes
Authors: Du Peng , Yu Jae Su 
Published: September 2017

AbstractA series of novel Eu3+-activated La2MoO6-La2WO6 red-emitting phosphors have been successfully prepared by a citrate-assisted sol-gel process. Both photoluminescence excitation and emission spectra suggest that the resultant products have the strong ultrabroad absorption band ranging from 220 to 450 nm. Under the excitation of 379 nm, the characteristic emissions of Eu3+ ions corresponding to the 5D0 → 7F
J
transitions are observed in the doped samples. The optimal doping concentration for Eu3+ ions is found to be 12 mol% and the quenching mechanism is attributed to the dipole-dipole interaction. A theoretical calculation based on the Judd-Ofelt theory is carried out to explore the local structure environment around the Eu3+ ions. The studied samples exhibit a typical thermal quenching effect with a T0.5 value of 338 K and the activation energy is determined to be 0.427 eV. A near-ultraviolet (NUV)-based white light-emitting diode (LED) is packaged by integrating a mixture of resultant phosphors, commercial blue-emitting and green-emitting phosphors into an NUV LED chip. The fabricated LED device emits glaring white light with high color rendering index (84.6) and proper correlated color temperature (6492 K). These results demonstrate that the Eu3+-activated La2MoO6-La2WO6 compounds are a promising candidate for indoor lighting as red-emitting phosphors.
High accuracy label-free classification of single-cell kinetic states from holographic cytometry of human melanoma cells
Authors: Hejna Miroslav , Jorapur Aparna , Song Jun S. , Judson Robert L. 
Published: September 2017

AbstractDigital holographic cytometry (DHC) permits label-free visualization of adherent cells. Dozens of cellular features can be derived from segmentation of hologram-derived images. However, the accuracy of single cell classification by these features remains limited for most applications, and lack of standardization metrics has hindered independent experimental comparison and validation. Here we identify twenty-six DHC-derived features that provide biologically independent information across a variety of mammalian cell state transitions. When trained on these features, machine-learning algorithms achieve blind single cell classification with up to 95% accuracy. Using classification accuracy to guide platform optimization, we develop methods to standardize holograms for the purpose of kinetic single cell cytometry. Applying our approach to human melanoma cells treated with a panel of cancer therapeutics, we track dynamic changes in cellular behavior and cell state over time. We provide the methods and computational tools for optimizing DHC for kinetic single adherent cell classification.
Vagus Nerve Stimulation Paired with Tones for the Treatment of Tinnitus: A Prospective Randomized Double-blind Controlled Pilot Study in Humans
Authors: Tyler Richard , Cacace Anthony , Stocking Christina , Tarver Brent , Engineer Navzer , Martin Jeffrey , Deshpande Aniruddha , Stecker Nancy , Pereira Melissa , Kilgard Michael , Burress Chester , Pierce David , Rennaker Robert , Vanneste Sven 
Published: September 2017

AbstractThe aim of the pilot study was to evaluate the effect of Vagus Nerve Stimulation (VNS) paired with sounds in chronic tinnitus patients. All participants were implanted and randomized to a paired VNS (n = 16) or control (n = 14) group. After 6 weeks of home therapy, all participants received paired VNS. The device was used on 96% of days with good compliance. After 6 weeks, the paired VNS group improved on the Tinnitus Handicap Inventory (THI) (p = 0.0012) compared to controls (p = 0.1561). The between-group difference was 10.3% (p = 0.3393). Fifty percent of the participants in the paired VNS group showed clinically meaningful improvements compared to 28% in controls. At one year, 50% of participants had a clinically meaningful response. The therapy had greater benefits for participants with tonal and non-blast induced tinnitus at the end of 6 (24.3% vs. 2%, p = 0.05) and 12 weeks (34% vs. 2%, p = 0.004) compared to controls with 80% and 70% responding at 6 months and 1 year, respectively. Adverse effects were mild and well-tolerated and the therapy had a similar safety profile to VNS for epilepsy. VNS paired with tones may be effective for a subgroup of tinnitus patients and provides impetus for a larger pivotal study.