bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractThe 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

AbstractSubstituted 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

AbstractThe 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

AbstractHeterochromatin 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

AbstractTranscriptional 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

AbstractAerotaxis 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

AbstractSurface 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

AbstractThe 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.
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

AbstractDynamic 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.
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

AbstractAutonomic 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

AbstractCancer 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

AbstractWe 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

AbstractThe 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

AbstractNicotinamide 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

AbstractWe 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

AbstractOviductosomes (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.