bluuebunny/crossref_metadata_2025 huggingface dataset:
circRNA_104075 stimulates YAP-dependent tumorigenesis through the regulation of HNF4a and may serve as a diagnostic marker in hepatocellular carcinoma
Authors: Zhang Xiao , Xu Yanfeng , Qian Zijun , Zheng Weisheng , Wu Qi , Chen Yan , Zhu Guoqing , Liu Ya , Bian Zhixuan , Xu Wen , Zhang Yue , Sun Fenyong , Pan Qiuhui , Wang Jiayi , Du Lutao , Yu Yongchun
Published: October 2018

Some types of circular RNA (circRNA) are aberrantly expressed in human diseases including hepatocellular carcinoma (HCC). However, its regulation mechanism and diagnostic roles are largely unknown. Here, we identified that circRNA_104075 (circ_104075) was highly expressed in HCC tissues, cell lines and serum. Mechanistically, HNF4a bound to the −1409 to −1401 region of the circ_104075 promoter to stimulate the expression of circ_104075. Moreover, circ_104075 acted as a ceRNA to upregulate YAP expression by absorbing miR-582-3p. Interestingly, an N6-methyladenosine (m6A) motif was identified in the 353–357 region of YAP 3′UTR, and this m6A modification was essential for the interaction between miR-582-3p and YAP 3′UTR. Further, the diagnostic performance of circ_104075 was evaluated. The area under the receiver operating characteristic (AUC-ROC) for circ_104075 was 0.973 with a sensitivity of 96.0% and a specificity of 98.3%. Collectively, we determined that circ_104075 was highly expressed in HCC and elucidated its upstream and downstream regulatory mechanisms. circ_104075 additionally has the potential to serve as a new diagnostic biomarker in HCC. Targeting circ_104075 may provide new strategies in HCC diagnosis and therapy.
Interfacing nickel nitride and nickel boosts both electrocatalytic hydrogen evolution and oxidation reactions
Authors: Song Fuzhan , Li Wei , Yang Jiaqi , Han Guanqun , Liao Peilin , Sun Yujie
Published: October 2018

Electrocatalysts of the hydrogen evolution and oxidation reactions (HER and HOR) are of critical importance for the realization of future hydrogen economy. In order to make electrocatalysts economically competitive for large-scale applications, increasing attention has been devoted to developing noble metal-free HER and HOR electrocatalysts especially for alkaline electrolytes due to the promise of emerging hydroxide exchange membrane fuel cells. Herein, we report that interface engineering of Ni3N and Ni results in a unique Ni3N/Ni electrocatalyst which exhibits exceptional HER/HOR activities in aqueous electrolytes. A systematic electrochemical study was carried out to investigate the superior hydrogen electrochemistry catalyzed by Ni3N/Ni, including nearly zero overpotential of catalytic onset, robust long-term durability, unity Faradaic efficiency, and excellent CO tolerance. Density functional theory computations were performed to aid the understanding of the electrochemical results and suggested that the real active sites are located at the interface between Ni3N and Ni.
Architecture of gene regulatory networks controlling flower development in Arabidopsis thaliana
Authors: Chen Dijun , Yan Wenhao , Fu Liang-Yu , Kaufmann Kerstin
Published: October 2018

Floral homeotic transcription factors (TFs) act in a combinatorial manner to specify the organ identities in the flower. However, the architecture and the function of the gene regulatory network (GRN) controlling floral organ specification is still poorly understood. In particular, the interconnections of homeotic TFs, microRNAs (miRNAs) and other factors controlling organ initiation and growth have not been studied systematically so far. Here, using a combination of genome-wide TF binding, mRNA and miRNA expression data, we reconstruct the dynamic GRN controlling floral meristem development and organ differentiation. We identify prevalent feed-forward loops (FFLs) mediated by floral homeotic TFs and miRNAs that regulate common targets. Experimental validation of a coherent FFL shows that petal size is controlled by the SEPALLATA3-regulated miR319/TCP4 module. We further show that combinatorial DNA-binding of homeotic factors and selected other TFs is predictive of organ-specific patterns of gene expression. Our results provide a valuable resource for studying molecular regulatory processes underlying floral organ specification in plants.
Calcium sensing by the STIM1 ER-luminal domain
Authors: Gudlur Aparna , Zeraik Ana Eliza , Hirve Nupura , Rajanikanth V. , Bobkov Andrey A. , Ma Guolin , Zheng Sisi , Wang Youjun , Zhou Yubin , Komives Elizabeth A. , Hogan Patrick G.
Published: October 2018

Stromal interaction molecule 1 (STIM1) monitors ER-luminal Ca2+ levels to maintain cellular Ca2+ balance and to support Ca2+ signalling. The prevailing view has been that STIM1 senses reduced ER Ca2+ through dissociation of bound Ca2+ from a single EF-hand site, which triggers a dramatic loss of secondary structure and dimerization of the STIM1 luminal domain. Here we find that the STIM1 luminal domain has 5–6 Ca2+-binding sites, that binding at these sites is energetically coupled to binding at the EF-hand site, and that Ca2+ dissociation controls a switch to a second structured conformation of the luminal domain rather than protein unfolding. Importantly, the other luminal-domain Ca2+-binding sites interact with the EF-hand site to control physiological activation of STIM1 in cells. These findings fundamentally revise our understanding of physiological Ca2+ sensing by STIM1, and highlight molecular mechanisms that govern the Ca2+ threshold for activation and the steep Ca2+ concentration dependence.
Structure and pro-toxic mechanism of the human Hsp90/PPIase/Tau complex
Authors: Oroz Javier , Chang Bliss J. , Wysoczanski Piotr , Lee Chung-Tien , Pérez-Lara Ángel , Chakraborty Pijush , Hofele Romina V. , Baker Jeremy D. , Blair Laura J. , Biernat Jacek , Urlaub Henning , Mandelkow Eckhard , Dickey Chad A. , Zweckstetter Markus
Published: October 2018

The molecular chaperone Hsp90 is critical for the maintenance of cellular homeostasis and represents a promising drug target. Despite increasing knowledge on the structure of Hsp90, the molecular basis of substrate recognition and pro-folding by Hsp90/co-chaperone complexes remains unknown. Here, we report the solution structures of human full-length Hsp90 in complex with the PPIase FKBP51, as well as the 280 kDa Hsp90/FKBP51 complex bound to the Alzheimer’s disease-related protein Tau. We reveal that the FKBP51/Hsp90 complex, which synergizes to promote toxic Tau oligomers in vivo, is highly dynamic and stabilizes the extended conformation of the Hsp90 dimer resulting in decreased Hsp90 ATPase activity. Within the ternary Hsp90/FKBP51/Tau complex, Hsp90 serves as a scaffold that traps the PPIase and nucleates multiple conformations of Tau’s proline-rich region next to the PPIase catalytic pocket in a phosphorylation-dependent manner. Our study defines a conceptual model for dynamic Hsp90/co-chaperone/client recognition.
syn-Selective alkylarylation of terminal alkynes via the combination of photoredox and nickel catalysis
Authors: Guo Lei , Song Fan , Zhu Shengqing , Li Huan , Chu Lingling
Published: October 2018

Substituted alkenes are pivotal structural motifs found in pharmaceuticals and agrochemicals. Although numerous methods have been developed to construct substituted alkenes, a generally efficient, mild, catalytic platform for the conversion of alkynes to this highly functionalized scaffold via successive C–C bond forming steps remains in high demand. Here we describe an intermolecular, regio- and syn-stereoselective alkylarylation of terminal alkynes with tertiary alkyl oxalates via photoredox-Ni dual catalysis. This catalytic protocol, synergistically combining Ir/Ni-catalyzed alkyne difunctionalization with photoinduced alkene isomerization, affords trisubstituted alkenes with excellent efficiency and syn-stereoselectivity. The mild conditions tolerate many functional groups, allowing for a broad scope with respect to terminal alkynes, aryl bromides, and alkyl oxalates.
Dual-gate organic phototransistor with high-gain and linear photoresponse
Authors: Chow Philip C. Y. , Matsuhisa Naoji , Zalar Peter , Koizumi Mari , Yokota Tomoyuki , Someya Takao
Published: October 2018

The conversion of light into electrical signal in a photodetector is a crucial process for a wide range of technological applications. Here we report a new device concept of dual-gate phototransistor that combines the operation of photodiodes and phototransistors to simultaneously enable high-gain and linear photoresponse without requiring external circuitry. In an oppositely biased, dual-gate transistor based on a solution-processed organic heterojunction layer, we find that the presence of both n- and p-type channels enables both photogenerated electrons and holes to efficiently separate and transport in the same semiconducting layer. This operation enables effective control of trap carrier density that leads to linear photoresponse with high photoconductive gain and a significant reduction of electrical noise. As we demonstrate using a large-area, 8 × 8 imaging array of dual-gate phototransistors, this device concept is promising for high-performance and scalable photodetectors with tunable dynamic range.
Arabidopsis AGDP1 links H3K9me2 to DNA methylation in heterochromatin
Authors: Zhang Cuijun , Du Xuan , Tang Kai , Yang Zhenlin , Pan Li , Zhu Peipei , Luo Jinyan , Jiang Yuwei , Zhang Hui , Wan Huafang , Wang Xingang , Wu Fengkai , Tao W. Andy , He Xin-Jian , Zhang Heng , Bressan Ray A. , Du Jiamu , Zhu Jian-Kang
Published: October 2018

Heterochromatin is a tightly packed form of chromatin that is associated with DNA methylation and histone 3 lysine 9 methylation (H3K9me). Here, we identify an H3K9me2-binding protein, Agenet domain (AGD)-containing p1 (AGDP1), in Arabidopsis thaliana. Here we find that AGDP1 can specifically recognize the H3K9me2 mark by its three pairs of tandem AGDs. We determine the crystal structure of the Agenet domain 1 and 2 cassette (AGD12) of Raphanus sativus AGDP1 in complex with an H3K9me2 peptide. In the complex, the histone peptide adopts a unique helical conformation. AGD12 specifically recognizes the H3K4me0 and H3K9me2 marks by hydrogen bonding and hydrophobic interactions. In addition, we find that AGDP1 is required for transcriptional silencing, non-CG DNA methylation, and H3K9 dimethylation at some loci. ChIP-seq data show that AGDP1 preferentially occupies long transposons and is associated with heterochromatin marks. Our findings suggest that, as a heterochromatin-binding protein, AGDP1 links H3K9me2 to DNA methylation in heterochromatin regions.
PRMT2 links histone H3R8 asymmetric dimethylation to oncogenic activation and tumorigenesis of glioblastoma
Authors: Dong Feng , Li Qian , Yang Chao , Huo Dawei , Wang Xing , Ai Chunbo , Kong Yu , Sun Xiaoyu , Wang Wen , Zhou Yan , Liu Xing , Li Wei , Gao Weiwei , Liu Wen , Kang Chunsheng , Wu Xudong
Published: October 2018

Transcriptional deregulation has a vital role in glioblastoma multiforme (GBM). Thus, identification of epigenetic modifiers essential for oncogenic transcriptional programs is a key to designing effective therapeutics for this deadly disease. Here we report that Protein Arginine Methyltransferase 2 (PRMT2) is highly expressed in GBM and correlated with poor prognosis. The silencing or inactivation of PRMT2 inhibits GBM cell growth and glioblastoma stem cell self-renewal in vitro, and suppresses orthotopic tumor growth, accompanied with significant deregulation of genes mainly associated with cell cycle progression and pathways in cancer. Mechanistically PRMT2 is responsible for H3R8 asymmetric methylation (H3R8me2a), whose enrichment at promoters and enhancers is closely correlated with known active histone marks and is required for the maintenance of target gene expression. Together, this study demonstrates that PRMT2 acts as a transcriptional co-activator for oncogenic gene expression programs in GBM pathogenesis and provides a rationale for PRMT2 targeting in aggressive gliomas.
Redox regulation of EGFR steers migration of hypoxic mammary cells towards oxygen
Authors: Deygas Mathieu , Gadet Rudy , Gillet Germain , Rimokh Ruth , Gonzalo Philippe , Mikaelian Ivan
Published: October 2018

Aerotaxis or chemotaxis to oxygen was described in bacteria 130 years ago. In eukaryotes, the main adaptation to hypoxia currently described relies on HIF transcription factors. To investigate whether aerotaxis is conserved in higher eukaryotes, an approach based on the self-generation of hypoxia after cell confinement was developed. We show that epithelial cells from various tissues migrate with an extreme directionality towards oxygen to escape hypoxia, independently of the HIF pathway. We provide evidence that, concomitant to the oxygen gradient, a gradient of reactive oxygen species (ROS) develops under confinement and that antioxidants dampen aerotaxis. Finally, we establish that in mammary cells, EGF receptor, the activity of which is potentiated by ROS and inhibited by hypoxia, represents the molecular target that guides hypoxic cells to oxygen. Our results reveals that aerotaxis is a property of higher eukaryotic cells and proceeds from the conversion of oxygen into ROS.
Correcting coherent errors with surface codes
Authors: Bravyi Sergey , Englbrecht Matthias , König Robert , Peard Nolan
Published: October 2018

Surface codes are building blocks of quantum computing platforms based on 2D arrays of qubits responsible for detecting and correcting errors. The error suppression achieved by the surface code is usually estimated by simulating toy noise models describing random Pauli errors. However, Pauli noise models fail to capture coherent processes such as systematic unitary errors caused by imperfect control pulses. Here we report the first large-scale simulation of quantum error correction protocols based on the surface code in the presence of coherent noise. We observe that the standard Pauli approximation provides an accurate estimate of the error threshold but underestimates the logical error rate in the sub-threshold regime. We find that for large code size the logical-level noise is well approximated by random Pauli errors even though the physical-level noise is coherent. Our work demonstrates that coherent effects do not significantly change the error correcting threshold of surface codes. This gives more confidence in the viability of the fault-tolerance architecture pursued by several experimental groups.
A recombinant conjugated pneumococcal vaccine that protects against murine infections with a similar efficacy to Prevnar-13
Authors: Reglinski Mark , Ercoli Giuseppe , Plumptre Charlie , Kay Emily , Petersen Fernanda C. , Paton James C. , Wren Brendan W. , Brown Jeremy S.
Published: October 2018

The pneumococcal conjugate vaccine (PCV) strongly protects against vaccine serotypes, but the rapid expansion of non-vaccine serotype disease and the vaccine’s high expense has reduced its overall impact. We have developed Protein Glycan Coupling Technology (PGCT) as a flexible methodology for making low-cost polysaccharide/protein glycoconjugates recombinantly inEscherichia coli. We have used PGCT to make a recombinant PCV containing serotype 4 capsular polysaccharide linked to theStreptococcus pneumoniaeproteins NanA, PiuA, and Sp0148. The introduction of theCampylobacter jejuniUDP-glucose 4-epimerase gene GalE (gne) intoE. coliimproved the yield of the resulting glycoprotein. PGCT glycoconjugate vaccination generated strong antibody responses in mice to both the capsule and the carrier protein antigens, with the PiuA/capsule glycoconjugate inducing similar anti-capsular antibody responses as the commercial PCV Prevnar-13. Antibody responses to PGCT glycoconjugates opsonisedS. pneumoniaeandStreptococcus mitisexpressing the serotype 4 capsule and promoted neutrophil phagocytosis ofS. pneumoniaeto a similar level as antisera generated by vaccination with Prevnar-13. Vaccination with the PGCT glycoconjugates protected mice against meningitis and septicaemia with the same efficacy as vaccination with Prevnar-13. In addition, vaccination with the protein antigen components from PGCT glycoconjugates alone provided partial protection against septicaemia and colonisation. These data demonstrate that a vaccine made by PGCT is as effective as Prevnar-13, identifies PiuA as a carrier protein for glycoconjugate vaccines, and demonstrates that linking capsular antigen toS. pneumoniaeprotein antigens has additional protective benefits that could provide a degree of serotype-independent immunity.
Author Correction: Iscador Qu inhibits doxorubicin-induced senescence of MCF7 cells
Authors: Srdic-Rajic Tatjana , Santibañez Juan F. , Kanjer Ksenija , Tisma-Miletic Nevena , Cavic Milena , Galun Daniel , Jevric Marko , Kardum Nevena , Konic-Ristic Aleksandra , Zoranovic Tamara
Published: October 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Publisher Correction: 3D Shape Modeling for Cell Nuclear Morphological Analysis and Classification
Authors: Kalinin Alexandr A. , Allyn-Feuer Ari , Ade Alex , Fon Gordon-Victor , Meixner Walter , Dilworth David , Husain Syed S. , de Wet Jeffrey R. , Higgins Gerald A. , Zheng Gen , Creekmore Amy , Wiley John W. , Verdone James E. , Veltri Robert W. , Pienta Kenneth J. , Coffey Donald S. , Athey Brian D. , Dinov Ivo D.
Published: October 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Cardiac troponins may be irreversibly modified by glycation: novel potential mechanisms of cardiac performance modulation
Authors: Janssens Johannes V. , Ma Brendan , Brimble Margaret A. , Van Eyk Jennifer E. , Delbridge Lea M. D. , Mellor Kimberley M.
Published: October 2018

Dynamic movements of the cardiac troponin complex are an important component of the cardiac cycle. Whether cardiac troponins are subjected to irreversible advanced glycation end-product (AGE) modification is unknown. This study interrogated human and rat cardiac troponin-C, troponin-I and troponin-T to identify endogenous AGE modifications using mass spectrometry (LC-MS/MS). AGE modifications were detected on two amino acid residues of human troponin-C (Lys6, Lys39), thirteen troponin-I residues (Lys36, Lys50, Lys58, Arg79, Lys117, Lys120, Lys131, Arg148, Arg162, Lys164, Lys183, Lys193, Arg204), and three troponin-T residues (Lys107, Lys125, Lys227). AGE modifications of three corresponding troponin-I residues (Lys58, Lys120, Lys194) and two corresponding troponin-T residues (Lys107, Lys227) were confirmed in cardiac tissue extracts from an experimental rodent diabetic model. Additionally, novel human troponin-I phosphorylation sites were detected (Thr119, Thr123). Accelerated AGE modification of troponin-C was evident in vitro with hexose sugar exposure. This study provides the first demonstration of the occurrence of cardiac troponin complex AGE-modifications. These irreversible AGE modifications are situated in regions of the troponin complex known to be important in myofilament relaxation, and may be of particular pathological importance in the pro-glycation environment of diabetic cardiomyopathy.
Publisher Correction: Experimental Zika Virus Infection in the Pregnant Common Marmoset Induces Spontaneous Fetal Loss and Neurodevelopmental Abnormalities
Authors: Seferovic Maxim , Sánchez-San Martín Claudia , Tardif Suzette D. , Rutherford Julienne , Castro Eumenia C. C. , Li Tony , Hodara Vida L. , Parodi Laura M. , Giavedoni Luis , Layne-Colon Donna , Tamhankar Manasi , Yagi Shigeo , Martyn Calla , Reyes Kevin , Suter Melissa A. , Aagaard Kjersti M. , Chiu Charles Y. , Patterson Jean L.
Published: October 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Waist-Stature Ratio And Its Relationship With Autonomic Recovery From Aerobic Exercise In Healthy Men
Authors: Fontes Anne Michelli G. G. , de Oliveira Letícia S. , Vanderlei Franciele M. , Garner David M. , Valenti Vitor E.
Published: October 2018

Autonomic modulation and cardiorespiratory variables are influenced by numerous factors, including anthropometric variables. We investigated autonomic recovery following aerobic exercise in healthy men with different waist-stature ratio (WSR) values. The study was conducted with 52 healthy men aged 18 to 30 years, divided into groups according to the WSR: G1 – between 0.40 and 0.449 (N = 19), G2 – between 0.45 and 0.50 (N = 28) and G3 – between 0.5 and 0.56 (N = 5). The subjects endured 15 minutes seated and at rest followed by an aerobic exercise and then remained seated for 60 minutes and at rest during recovery from exercise. Heart rate (HR) variability (HRV) (rMSSD, SD1, HF [ms2]) and cardiorespiratory variables were analyzed before and after exercise. Recovery of respiratory rate, diastolic blood pressure, SD1 and HF indices were delayed in G2. G3 presented delayed recovery after the maximal effort test while no difference with G2 was noted in the moderate intensity. Correlation and linear regression analysis indicated association of WSR, body mass index and waist circumference with HRV indices in the recovery from aerobic exercise (45 to 60 minutes after exercise) in G2. In conclusion, healthy men with higher WSR accomplished delayed autonomic recovery following maximal effort exercise.
Oxytetracycline have the therapeutic efficiency in CD133+ HCC population through suppression CD133 expression by decreasing of protein stability of CD133
Authors: Song Yeonhwa , Kim In-Ki , Choi Inhee , Kim Se-Hyuk , Seo Haeng Ran
Published: October 2018

Cancer stem cells (CSCs) are considered a serious sub-population in cancer tissues because of their strong resistance to conventional chemotherapy and radiotherapy. Thus, the current advancements in the use of liver cancer stem cells (LCSC) to develop efficient and organized means to an antitumor agent is quickly gaining recognition as a novel goal. Previously, we characterized CSCs in primary hepatocellular carcinoma (HCC) and identified CD133 as a CSC cell-surface marker. In this study, we proposed to use non-target based high throughput screening (HTS) approach to specifically target AFP+/CD133+ HCC present in mixed populations of HCC cells with hepatocytes. Through screening, we identified oxytetracycline, which showed significant inhibition activity of LCSC population without damage on hepatocytes. To determine whether oxytetracycline targets LCSC, we examined whether oxytetracycline treatment could change the CD133 expression, spheroid forming ability as well as the levels of stem cell-related markers. Treatment of spheroid-forming LCSC with oxytetracycline effectively decreased the spheroid formation and the CD133+ cell population. oxytetracycline could suppress expression of CD133 without changing of expression of other stem cell-related markers. Importantly, these series of phenomena by oxytetracycline occurs because of alteration of CD133 protein stability by oxytetracycline. Alterations in the malignant properties of AFP+/CD133+ HCC by oxytetracycline were also investigated by xenograft assay in nude mice. Treatment of oxytetracycline significantly attenuated tumor formation and CD133+ cell population in xenograft mice. These results indicate that the oxytetracycline suppresses stemness and malignancies in HCC cells through destabilization of CD133 in LCSC population, providing novel therapeutic strategies targeting specifically cancer stem-like cells.
Ultra-Broadband Acoustic Diode in Open Bend Tunnel by Negative Reflective Metasurface
Authors: Liang Qingxuan , Cheng Yong , He Jin , Chang Jinke , Chen Tianning , Li Dichen
Published: October 2018

We theoretically and numerically propose an open bend tunnel with the capability of realizing ultra-broadband unidirectional transmission. The designed tunnel can isolate acoustic wave incidence from opposite directions and substance like the fluids or objects can exchange freely by employing acoustic gradient metasurface. The underlying mechanism is due to apparent negative reflection in ultra-broadband frequency range when the incoming angle impinging on the metasurface is over the critical incidence. The numerical results keep a good agreement with the theoretical analyses. The proposed design could be employed to generate various situations, like broadband noise control, architectural acoustics and ultrasound imaging.
Differential expression of immune receptors in two marine sponges upon exposure to microbial-associated molecular patterns
Authors: Pita Lucía , Hoeppner Marc P. , Ribes Marta , Hentschel Ute
Published: October 2018

The innate immune system helps animals to navigate the microbial world. The response to microbes relies on the specific recognition of microbial-associated molecular patterns (MAMPs) by immune receptors. Sponges (phylum Porifera), as early-diverging animals, provide insights into conserved mechanisms for animal-microbe crosstalk. However, experimental data is limited. We adopted an experimental approach followed by RNA-Seq and differential gene expression analysis in order to characterise the sponge immune response. Two Mediterranean species, Aplysina aerophoba and Dysidea avara, were exposed to a “cocktail” of MAMPs (lipopolysaccharide and peptidoglycan) or to sterile artificial seawater (control) and sampled 1 h, 3 h, and 5 h post-treatment for RNA-Seq. The response involved, first and foremost, a higher number of differentially-expressed genes in A. aerophoba than D. avara. Secondly, while both species constitutively express a diverse repertoire of immune receptors, they differed in their expression profiles upon MAMP challenge. The response in D. avara was mediated by increased expression of two NLR genes, whereas the response in A. aerophoba involved SRCR and GPCR genes. From the set of annotated genes we infer that both species activated apoptosis in response to MAMPs while in A. aerophoba phagocytosis was additionally stimulated. Our study assessed for the first time the transcriptomic responses of sponges to MAMPs and revealed conserved and species-specific features of poriferan immunity as well as genes potentially relevant to animal-microbe interactions.
The nanomolar sensing of nicotinamide adenine dinucleotide in human plasma using a cycling assay in albumin modified simulated body fluids
Authors: Brunnbauer Philipp , Leder Annekatrin , Kamali Can , Kamali Kaan , Keshi Eriselda , Splith Katrin , Wabitsch Simon , Haber Philipp , Atanasov Georgi , Feldbrügge Linda , Sauer Igor M. , Pratschke Johann , Schmelzle Moritz , Krenzien Felix
Published: October 2018

Nicotinamide adenine dinucleotide (NAD), a prominent member of the pyridine nucleotide family, plays a pivotal role in cell-oxidation protection, DNA repair, cell signalling and central metabolic pathways, such as beta oxidation, glycolysis and the citric acid cycle. In particular, extracellular NAD+ has recently been demonstrated to moderate pathogenesis of multiple systemic diseases as well as aging. Herein we present an assaying method, that serves to quantify extracellular NAD+ in human heparinised plasma and exhibits a sensitivity ranging from the low micromolar into the low nanomolar domain. The assay achieves the quantification of extracellular NAD+ by means of a two-step enzymatic cycling reaction, based on alcohol dehydrogenase. An albumin modified revised simulated body fluid was employed as standard matrix in order to optimise enzymatic activity and enhance the linear behaviour and sensitivity of the method. In addition, we evaluated assay linearity, reproducibility and confirmed long-term storage stability of extracellular NAD+ in frozen human heparinised plasma. In summary, our findings pose a novel standardised method suitable for high throughput screenings of extracellular NAD+ levels in human heparinised plasma, paving the way for new clinical discovery studies.
Partition of energy for a dissipative quantum oscillator
Authors: Bialas P. , Spiechowicz J. , Łuczka J.
Published: October 2018

We reveal a new face of the old clichéd system: a dissipative quantum harmonic oscillator. We formulate and study a quantum counterpart of the energy equipartition theorem satisfied for classical systems. Both mean kinetic energy Ek and mean potential energy Ep of the oscillator are expressed as Ek = 〈εk〉 and Ep = 〈εp〉, where 〈εk〉 and 〈εp〉 are mean kinetic and potential energies per one degree of freedom of the thermostat which consists of harmonic oscillators too. The symbol 〈...〉 denotes two-fold averaging: (i) over the Gibbs canonical state for the thermostat and (ii) over thermostat oscillators frequencies ω which contribute to Ek and Ep according to the probability distribution $${{\mathbb{P}}}_{k}(\omega )$$

ℙ

k

(
ω
)
and $${{\mathbb{P}}}_{p}(\omega )$$

ℙ

p

(
ω
)
, respectively. The role of the system-thermostat coupling strength and the memory time is analysed for the exponentially decaying memory function (Drude dissipation mechanism) and the algebraically decaying damping kernel.
Murine Oviductosomes (OVS) microRNA profiling during the estrous cycle: Delivery of OVS-borne microRNAs to sperm where miR-34c-5p localizes at the centrosome
Authors: Fereshteh Zeinab , Schmidt Skye A. , Al-Dossary Amal A. , Accerbi Monica , Arighi Cecilia , Cowart Julie , Song Jia L. , Green Pamela J. , Choi Kyungmin , Yoo Soonmoon , Martin-DeLeon Patricia A.
Published: October 2018

Oviductosomes (OVS) are nano-sized extracellular vesicles secreted in the oviductal luminal fluid by oviductal epithelial cells and known to be involved in sperm capacitation and fertility. Although they have been shown to transfer encapsulated proteins to sperm, cargo constituents other than proteins have not been identified. Using next-generation sequencing, we demonstrate that OVS are carriers of microRNAs (miRNAs), with 272 detected throughout the estrous cycle. Of the 50 most abundant, 6 (12%) and 2 (4%) were expressed at significantly higher levels (P < 0.05) at metestrus/diestrus and proestrus/estrus. RT-qPCR showed that selected miRNAs are present in oviductal epithelial cells in significantly (P < 0.05) lower abundance than in OVS, indicating selective miRNA packaging. The majority (64%) of the top 25 OVS miRNAs are present in sperm. These miRNAs’ potential target list is enriched with transcription factors, transcription regulators, and protein kinases and there are several embryonic developmentally-related genes. Importantly, OVS can deliver to sperm miRNAs, including miR-34c-5p which is essential for the first cleavage and is solely sperm-derived in the zygote. Z-stack of confocal images of sperm co-incubated with OVS loaded with labeled miRNAs showed the intracellular location of the delivered miRNAs. Interestingly, individual miRNAs were predominantly localized in specific head compartments, with miR-34c-5p being highly concentrated at the centrosome where it is known to function. These results, for the first time, demonstrate OVS’ ability to contribute to the sperm’s miRNA repertoire (an important role for solely sperm-derived zygotic miRNAs) and the physiological relevance of an OVS-borne miRNA that is delivered to sperm.
Corticohippocampal Dysfunction In The OBiden Mouse Model Of Primary Oligodendrogliopathy
Authors: Radecki Daniel Z. , Johnson Elizabeth L. , Brown Ashley K. , Meshkin Nicholas T. , Perrine Shane A. , Gow Alexander
Published: October 2018

Despite concerted efforts over decades, the etiology of multiple sclerosis (MS) remains unclear. Autoimmunity, environmental-challenges, molecular mimicry and viral hypotheses have proven equivocal because early-stage disease is typically presymptomatic. Indeed, most animal models of MS also lack defined etiologies. We have developed a novel adult-onset oligodendrogliopathy using a delineated metabolic stress etiology in myelinating cells, and our central question is, “how much of the pathobiology of MS can be recapitulated in this model?” The analyses described herein demonstrate that innate immune activation, glial scarring, cortical and hippocampal damage with accompanying electrophysiological, behavioral and memory deficits naturally emerge from disease progression. Molecular analyses reveal neurofilament changes in normal-appearing gray matter that parallel those in cortical samples from MS patients with progressive disease. Finally, axon initial segments of deep layer pyramidal neurons are perturbed in entorhinal/frontal cortex and hippocampus fromOBidenmice, and computational modeling provides insight into vulnerabilities of action potential generation during demyelination and early remyelination. We integrate these findings into a working model of corticohippocampal circuit dysfunction to predict how myelin damage might eventually lead to cognitive decline.
The HCV genome domains 5BSL3.1 and 5BSL3.3 act as managers of translation
Authors: Romero-López Cristina , Ríos-Marco Pablo , Berzal-Herranz Beatriz , Berzal-Herranz Alfredo
Published: October 2018

The RNA genome of the hepatitis C virus (HCV) encodes a single open reading frame (ORF) containing numerous functional elements. Among these, the cis-acting replication element (CRE) at the 3′ end of the viral ORF, has become of increasing interest given its dual role as a viral translation repressor and replication enhancer. Long-range RNA-RNA contacts mediated by the CRE build the structural scaffold required for its proper functioning. The recruitment of different cellular factors, many related to the functioning of the translation machinery, might aid in the CRE-exerted downregulation of viral translation. The present data show that the CRE promotes a defect in polysome production, and hinders the assembly of the 80S complex, likely through the direct, high affinity recruitment of the 40S ribosomal subunit. This interaction involves the highly conserved 5BSL3.1 and 5BSL3.3 domains of the CRE, and is strictly dependent on RNA-protein contacts, particularly with the ribosomal proteins RPSA and RPS29. These observations support a model in which the CRE-mediated inhibition of viral translation is a multifactorial process defined by the establishment of long-range RNA-RNA interactions between the 5′ and 3′ ends of the viral genome, the sequestration of the 40S subunit by the CRE, and the subsequent stalling of polysome elongation at the 3′ end of the ORF, all governed by the highly stable hairpin domains 5BSL3.1 and 5BSL3.3. The present data thus suggest a new managerial role in HCV translation for these 5BSL3.1 and 5BSL3.3 domains.
Enhanced spatial focusing increases feature-based selection in unattended locations
Authors: Bartsch Mandy V. , Donohue Sarah E. , Strumpf Hendrik , Schoenfeld Mircea A. , Hopf Jens-Max
Published: October 2018

Attention is a multifaceted phenomenon, which operates on features (e.g., colour or motion) and over space. A fundamental question is whether the attentional selection of features is confined to the spatially-attended location or operates independently across the entire visual field (global feature-based attention, GFBA). Studies providing evidence for GFBA often employ feature probes presented at spatially unattended locations, which elicit enhanced brain responses when they match a currently-attended target feature. However, the validity of this interpretation relies on consistent spatial focusing onto the target. If the probe were to temporarily attract spatial attention, the reported effects could reflect transient spatial selection processes, rather than GFBA. Here, using magnetoencephalographic recordings (MEG) in humans, we manipulate the strength and consistency of spatial focusing to the target by increasing the target discrimination difficulty (Experiment 1), and by demarcating the upcoming target’s location with a placeholder (Experiment 2), to see if GFBA effects are preserved. We observe that motivating stronger spatial focusing to the target did not diminish the effects of GFBA. Instead, aiding spatial pre-focusing with a placeholder enhanced the feature response at unattended locations. Our findings confirm that feature selection effects measured with spatially-unattended probes reflect a true location-independent neural bias.
N-glycan Remodeling Using Mannosidase Inhibitors to Increase High-mannose Glycans on Acid α-Glucosidase in Transgenic Rice Cell Cultures
Authors: Choi Hong-Yeol , Park Heajin , Hong Jong Kwang , Kim Sun-Dal , Kwon Jun-Young , You SeungKwan , Do Jonghye , Lee Dong-Yup , Kim Ha Hyung , Kim Dong-Il
Published: October 2018

Glycoengineering of plant expression systems is a prerequisite for the production of biopharmaceuticals that are compatible with animal-derived glycoproteins. Large amounts of high-mannose glycans such as Man7GlcNAc2, Man8GlcNAc2, and Man9GlcNAc2 (Man7/8/9), which can be favorably modified by chemical conjugation of mannose-6-phosphate, are desirable for lysosomal enzyme targeting. This study proposed a rice cell-based glycoengineering strategy using two different mannosidase inhibitors, kifunensine (KIF) and swainsonine (SWA), to increase Man7/8/9 glycoforms of recombinant human acid α-glucosidase (rhGAA), which is a therapeutic enzyme for Pompe disease. Response surface methodology was used to investigate the effects of the mannosidase inhibitors and to evaluate the synergistic effect of glycoengineering on rhGAA. Both inhibitors suppressed formation of plant-specific complex and paucimannose type N-glycans. SWA increased hybrid type glycans while KIF significantly increased Man7/8/9. Interestingly, the combination of KIF and SWA more effectively enhanced synthesis of Man7/8/9, especially Man9, than KIF alone. These changes show that SWA in combination with KIF more efficiently inhibited ER α-mannosidase II, resulting in a synergistic effect on synthesis of Man7/8/9. In conclusion, combined KIF and SWA treatment in rice cell culture media can be an effective method for the production of rhGAA displaying dominantly Man7/8/9 glycoforms without genetic manipulation of glycosylation.
Comparative analysis of the Pocillopora damicornis genome highlights role of immune system in coral evolution
Authors: Cunning R. , Bay R. A. , Gillette P. , Baker A. C. , Traylor-Knowles N.
Published: October 2018

Comparative analysis of the expanding genomic resources for scleractinian corals may provide insights into the evolution of these organisms, with implications for their continued persistence under global climate change. Here, we sequenced and annotated the genome of Pocillopora damicornis, one of the most abundant and widespread corals in the world. We compared this genome, based on protein-coding gene orthology, with other publicly available coral genomes (Cnidaria, Anthozoa, Scleractinia), as well as genomes from other anthozoan groups (Actiniaria, Corallimorpharia), and two basal metazoan outgroup phlya (Porifera, Ctenophora). We found that 46.6% of P. damicornis genes had orthologs in all other scleractinians, defining a coral ‘core’ genome enriched in basic housekeeping functions. Of these core genes, 3.7% were unique to scleractinians and were enriched in immune functionality, suggesting an important role of the immune system in coral evolution. Genes occurring only in P. damicornis were enriched in cellular signaling and stress response pathways, and we found similar immune-related gene family expansions in each coral species, indicating that immune system diversification may be a prominent feature of scleractinian coral evolution at multiple taxonomic levels. Diversification of the immune gene repertoire may underlie scleractinian adaptations to symbiosis, pathogen interactions, and environmental stress.
3D MALDI mass spectrometry imaging reveals specific localization of long-chain acylcarnitines within a 10-day time window of spinal cord injury
Authors: Quanico Jusal , Hauberg-Lotte Lena , Devaux Stephanie , Laouby Zahra , Meriaux Celine , Raffo-Romero Antonella , Rose Melanie , Westerheide Leia , Vehmeyer Jost , Rodet Franck , Maass Peter , Cizkova Dasa , Zilka Norbert , Cubinkova Veronika , Fournier Isabelle , Salzet Michel
Published: October 2018

We report, for the first time, the detection and specific localization of long-chain acylcarnitines (LC ACs) along the lesion margins in an experimental model of spinal cord injury (SCI) using 3D mass spectrometry imaging (MSI). Acylcarnitines palmitoylcarnitine (AC(16:0)), palmitoleoylcarnitine (AC(16:1)), elaidic carnitine (AC(18:1)) and tetradecanoylcarnitine (AC(14:1)) were detected as early as 3 days post injury, and were present along the lesion margins 7 and 10 days after SCI induced by balloon compression technique in the rat. 3D MSI revealed the heterogeneous distribution of these lipids across the injured spinal cord, appearing well-defined at the lesion margins rostral to the lesion center, and becoming widespread and less confined to the margins at the region located caudally. The assigned acylcarnitines co-localize with resident microglia/macrophages detected along the lesion margins by immunofluorescence. Given the reported pro-inflammatory role of these acylcarnitines, their specific spatial localization along the lesion margin could hint at their potential pathophysiological roles in the progression of SCI.
Polarization-resolved and polarization- multiplexed spike encoding properties in photonic neuron based on VCSEL-SA
Authors: Zhang Yahui , Xiang Shuiying , Guo Xingxing , Wen Aijun , Hao Yue
Published: October 2018

The spike encoding properties of two polarization-resolved modes in vertical-cavity surface-emitting laser with an embedded saturable absorber (VCSEL-SA) are investigated numerically, based on the spin-flip model combined with the Yamada model. The results show that the external input optical pulse (EIOP) can be encoded into spikes in X-polarization (XP) mode, Y-polarization (YP) mode, or both XP and YP modes. Furthermore, the numerical bifurcation diagrams show that a lower (higher) strength of EIOP is beneficial for generating tonic (phasic) spikes; a small amplitude anisotropy contributes to wide (narrow) tonic spiking range in XP (YP) mode; a large current leads to low thresholds of EIOP strength for both XP and YP modes. However, the spike encoding properties are hardly affected by the phase anisotropy. The encoding rate is shown to be improved by increasing EIOP strength. Moreover, dual-channel polarization-multiplexed spike encoding can also be achieved in a single VCSEL-SA. To the best of our knowledge, such single channel polarization-resolved and dual-channel polarization-multiplexed spike encoding schemes have not yet been reported. Hence, this work is valuable for ultrafast photonic neuromorphic systems and brain-inspired information processing.
An unconventional hydrogen effect that suppresses thermal formation of the hcp phase in fcc steels
Authors: Koyama Motomichi , Hirata Kenji , Abe Yuji , Mitsuda Akihiro , Iikubo Satoshi , Tsuzaki Kaneaki
Published: October 2018

Iron and steels are extensively used as structural materials, and have three primary phase structures: Body-centered cubic (bcc), face-centered cubic (fcc), and hexagonal closed-packed (hcp). Controlling phase stabilities, especially by the use of interstitials, is a universal method that provides a diverse variety of functional and mechanical properties in steels. In this context, hydrogen, which can act as an interstitial species in steels, has been recognized to promote phase transformation from fcc to hcp. However, we here report a dramatic effect of interstitial hydrogen that suppresses this hcp phase transformation. More specifically, the fraction of hcp phase that forms during cooling decreases with increasing diffusible hydrogen content. This new finding opens new venues for thermodynamics-based microstructure design and for development of robust, strong, and ductile steels in hydrogen-related infrastructures.
Biomedical applications of mid-infrared quantum cascade lasers – a review
Authors: Isensee Katharina , Kröger-Lui Niels , Petrich Wolfgang
Published: October 2018

Quantum cascade lasers with high spectral power density and narrow band emission profiles provide novel access to biomedical applications.
Fabricating a new electrochemically modified pencil graphite electrode based on acetophenone (2,4-dinitrophenyl)hydrazone for determining selenium in food and water samples
Authors: Azizi Zohreh , Babakhanian Arash
Published: October 2018

Determination of selenium compounds in air, soil, water, and food samples is of interest as selenium's bioavailability and toxicity depend on its concentration level.
A direct electron transfer biosensor based on a horseradish peroxidase and gold nanotriangle modified electrode and electrocatalysis
Authors: Niu Yanyan , Liu Juan , Chen Wei , Yin Chunxiao , Weng Wenju , Li Xiaoyan , Wang Xiaoling , Li Guangjiu , Sun Wei
Published: October 2018

Gold nanotriangles (AuNTs) were used as a modifier on the surface of a carbon ionic liquid electrode (CILE), which was applied to realize direct electrochemistry and electrocatalysis of horseradish peroxidase (HRP).
Single crystal growth and magnetic properties of the mixed valent Yb containing Zintl phase, Yb14MgSb11
Authors: Kunz Wille Elizabeth L. , Jo Na Hyun , Fettinger James C. , Canfield Paul C. , Kauzlarich Susan M.
Published: October 2018

Large crystals of Yb14MgSb11 prepared by Sn flux show the presence of Yb3+ making this compound a Zintl phase.
Recent advances in the synthesis of [a]-benzo-fused BODIPY fluorophores
Authors: Jean-Gérard Ludivine , Vasseur William , Scherninski François , Andrioletti Bruno
Published: October 2018

This feature article summarizes the different strategies for the synthesis of [a]-benzo-fused BODIPYs that have been reported in the literature until 2018.
From venoms to BBB-shuttles. MiniCTX3: a molecular vector derived from scorpion venom
Authors: Díaz-Perlas Cristina , Varese Monica , Guardiola Salvador , García Jesús , Sánchez-Navarro Macarena , Giralt Ernest , Teixidó Meritxell
Published: October 2018

A monocyclic peptidomimetic version of chlorotoxin, MiniCTX3, was developed as a BBB-shuttle being able to transport nanoparticles across endothelial cells. Our results reveal animal venoms as an outstanding source of BBB-shuttles.
Enhancing intracellular microRNA imaging: a new strategy combining double-channel exciting single colour fluorescence with the target cycling amplification reaction
Authors: Zhang Keying , Song Shuting , Yang Lin , Min Qianhao , Wu Xingcai , Zhu Jun-Jie
Published: October 2018

Enhancing microRNA imaging in living cells using double-channel exciting single colour fluorescence coupled with the target cycling amplification reaction.
Evaluation of the photo-degradation of Alzheimer's amyloid fibrils with a label-free approach
Authors: Wang Tianke , Zhang Liwei , Wang Jie , Feng Yonghai , Xu Enquan , Mao Xiaobo , Liu Lei
Published: October 2018

Quartz crystal microbalance is a useful method to quantitatively evaluate the degradation of Aβ fibrils by porphyrin under UV irradiation.
A robust monolithic metal–organic framework with hierarchical porosity
Authors: Vilela Sérgio M. F. , Salcedo-Abraira Pablo , Micheron Loïc , Solla Eugenio L. , Yot Pascal G. , Horcajada Patricia
Published: October 2018

Mechanically robust centimetric single-piece MOF monoliths with hierarchical porosity.
A reinforced Pickering emulsion for cascade reactions
Authors: Xue Nan , Zhang Gaihong , Zhang Xiaoming , Yang Hengquan
Published: October 2018

Based on an interfacial sol–gel process, a novel reinforced Pickering emulsion has been developed successfully for one-pot cascade reactions involving incompatible catalysts.
Facile preparation of phospholipid–amorphous calcium carbonate hybrid nanoparticles: toward controllable burst drug release and enhanced tumor penetration
Authors: Wang Cheng , Liu Xuerong , Chen Shaoqing , Hu Fuqiang , Sun Jihong , Yuan Hong
Published: October 2018

A hybrid system able to specifically realize water-responsive burst drug release and potentiate drug penetration into deep tumor tissues has been developed.
Antigen-responsive fluorescent antibody probes generated by selective N-terminal modification of IgGs
Authors: Fukunaga Keisuke , Watanabe Takayoshi , Novitasari Dian , Ohashi Hiroyuki , Abe Ryoji , Hohsaka Takahiro
Published: October 2018

Fluorescent antibody probes showing antigen-dependent fluorescence responses were developed by N-terminal-selective reductive alkylation of IgGs.