bluuebunny/crossref_metadata_2025_split huggingface dataset:
The induction and consequences of Influenza A virus-induced cell death
Authors: Atkin-Smith Georgia K. , Duan Mubing , Chen Weisan , Poon Ivan K. H. 
Published: September 2018

AbstractInfection with Influenza A virus (IAV) causes significant cell death within the upper and lower respiratory tract and lung parenchyma. In severe infections, high levels of cell death can exacerbate inflammation and comprise the integrity of the epithelial cell barrier leading to respiratory failure. IAV infection of airway and alveolar epithelial cells promotes immune cell infiltration into the lung and therefore, immune cell types such as macrophages, monocytes and neutrophils are readily exposed to IAV and infection-induced death. Although the induction of cell death through apoptosis and necrosis following IAV infection is a well-known phenomenon, the molecular determinants responsible for inducing cell death is not fully understood. Here, we review the current understanding of IAV-induced cell death and critically evaluate the consequences of cell death in aiding either the restoration of lung homoeostasis or the progression of IAV-induced lung pathologies.
Analysis of chromatin accessibility uncovers TEAD1 as a regulator of migration in human glioblastoma
Authors: Tome-Garcia Jessica , Erfani Parsa , Nudelman German , Tsankov Alexander M. , Katsyv Igor , Tejero Rut , Bin Zhang  , Walsh Martin , Friedel Roland H. , Zaslavsky Elena , Tsankova Nadejda M. 
Published: September 2018

AbstractThe intrinsic drivers of migration in glioblastoma (GBM) are poorly understood. To better capture the native molecular imprint of GBM and its developmental context, here we isolate human stem cell populations from GBM (GSC) and germinal matrix tissues and map their chromatin accessibility via ATAC-seq. We uncover two distinct regulatory GSC signatures, a developmentally shared/proliferative and a tumor-specific/migratory one in which TEAD1/4 motifs are uniquely overrepresented. Using ChIP-PCR, we validate TEAD1 trans occupancy at accessibility sites within AQP4, EGFR, and CDH4. To further characterize TEAD’s functional role in GBM, we knockout TEAD1 or TEAD4 in patient-derived GBM lines using CRISPR-Cas9. TEAD1 ablation robustly diminishes migration, both in vitro and in vivo, and alters migratory and EMT transcriptome signatures with consistent downregulation of its target AQP4. TEAD1 overexpression restores AQP4 expression, and both TEAD1 and AQP4 overexpression rescue migratory deficits in TEAD1-knockout cells, implicating a direct regulatory role for TEAD1–AQP4 in GBM migration.
Outward open conformation of a Major Facilitator Superfamily multidrug/H+ antiporter provides insights into switching mechanism
Authors: Nagarathinam Kumar , Nakada-Nakura Yoshiko , Parthier Christoph , Terada Tohru , Juge Narinobu , Jaenecke Frank , Liu Kehong , Hotta Yunhon , Miyaji Takaaki , Omote Hiroshi , Iwata So , Nomura Norimichi , Stubbs Milton T. , Tanabe Mikio 
Published: September 2018

AbstractMultidrug resistance (MDR) poses a major challenge to medicine. A principle cause of MDR is through active efflux by MDR transporters situated in the bacterial membrane. Here we present the crystal structure of the major facilitator superfamily (MFS) drug/H+ antiporter MdfA from Escherichia coli in an outward open conformation. Comparison with the inward facing (drug binding) state shows that, in addition to the expected change in relative orientations of the N- and C-terminal lobes of the antiporter, the conformation of TM5 is kinked and twisted. In vitro reconstitution experiments demonstrate the importance of selected residues for transport and molecular dynamics simulations are used to gain insights into antiporter switching. With the availability of structures of alternative conformational states, we anticipate that MdfA will serve as a model system for understanding drug efflux in MFS MDR antiporters.
Mechanotransduction is required for establishing and maintaining mature inner hair cells and regulating efferent innervation
Authors: Corns Laura F. , Johnson Stuart L. , Roberts Terri , Ranatunga Kishani M. , Hendry Aenea , Ceriani Federico , Safieddine Saaid , Steel Karen P. , Forge Andy , Petit Christine , Furness David N. , Kros Corné J. , Marcotti Walter 
Published: September 2018

AbstractIn the adult auditory organ, mechanoelectrical transducer (MET) channels are essential for transducing acoustic stimuli into electrical signals. In the absence of incoming sound, a fraction of the MET channels on top of the sensory hair cells are open, resulting in a sustained depolarizing current. By genetically manipulating the in vivo expression of molecular components of the MET apparatus, we show that during pre-hearing stages the MET current is essential for establishing the electrophysiological properties of mature inner hair cells (IHCs). If the MET current is abolished in adult IHCs, they revert into cells showing electrical and morphological features characteristic of pre-hearing IHCs, including the re-establishment of cholinergic efferent innervation. The MET current is thus critical for the maintenance of the functional properties of adult IHCs, implying a degree of plasticity in the mature auditory system in response to the absence of normal transduction of acoustic signals.
Multibandgap quantum dot ensembles for solar-matched infrared energy harvesting
Authors: Sun Bin , Ouellette Olivier , García de Arquer F. Pelayo , Voznyy Oleksandr , Kim Younghoon , Wei Mingyang , Proppe Andrew H. , Saidaminov Makhsud I. , Xu Jixian , Liu Mengxia , Li Peicheng , Fan James Z. , Jo Jea Woong , Tan Hairen , Tan Furui , Hoogland Sjoerd , Lu Zheng Hong , Kelley Shana O. , Sargent Edward H. 
Published: September 2018

AbstractAs crystalline silicon solar cells approach in efficiency their theoretical limit, strategies are being developed to achieve efficient infrared energy harvesting to augment silicon using solar photons from beyond its 1100 nm absorption edge. Herein we report a strategy that uses multi-bandgap lead sulfide colloidal quantum dot (CQD) ensembles to maximize short-circuit current and open-circuit voltage simultaneously. We engineer the density of states to achieve simultaneously a large quasi-Fermi level splitting and a tailored optical response that matches the infrared solar spectrum. We shape the density of states by selectively introducing larger-bandgap CQDs within a smaller-bandgap CQD population, achieving a 40 meV increase in open-circuit voltage. The near-unity internal quantum efficiency in the optimized multi-bandgap CQD ensemble yielded a maximized photocurrent of 3.7 ± 0.2 mA cm−2. This provides a record for silicon-filtered power conversion efficiency equal to one power point, a 25% (relative) improvement compared to the best previously-reported results.
Cell-specific proteome analyses of human bone marrow reveal molecular features of age-dependent functional decline
Authors: Hennrich Marco L. , Romanov Natalie , Horn Patrick , Jaeger Samira , Eckstein Volker , Steeples Violetta , Ye Fei , Ding Ximing , Poisa-Beiro Laura , Lai Mang Ching , Lang Benjamin , Boultwood Jacqueline , Luft Thomas , Zaugg Judith B. , Pellagatti Andrea , Bork Peer , Aloy Patrick , Gavin Anne-Claude , Ho Anthony D. 
Published: September 2018

AbstractDiminishing potential to replace damaged tissues is a hallmark for ageing of somatic stem cells, but the mechanisms remain elusive. Here, we present proteome-wide atlases of age-associated alterations in human haematopoietic stem and progenitor cells (HPCs) and five other cell populations that constitute the bone marrow niche. For each, the abundance of a large fraction of the ~12,000 proteins identified is assessed in 59 human subjects from different ages. As the HPCs become older, pathways in central carbon metabolism exhibit features reminiscent of the Warburg effect, where glycolytic intermediates are rerouted towards anabolism. Simultaneously, altered abundance of early regulators of HPC differentiation reveals a reduced functionality and a bias towards myeloid differentiation. Ageing causes alterations in the bone marrow niche too, and diminishes the functionality of the pathways involved in HPC homing. The data represent a valuable resource for further analyses, and for validation of knowledge gained from animal models.
Genome-wide discovery of somatic regulatory variants in diffuse large B-cell lymphoma
Authors: Arthur Sarah E. , Jiang Aixiang , Grande Bruno M. , Alcaide Miguel , Cojocaru Razvan , Rushton Christopher K. , Mottok Anja , Hilton Laura K. , Lat Prince Kumar , Zhao Eric Y. , Culibrk Luka , Ennishi Daisuke , Jessa Selin , Chong Lauren , Thomas Nicole , Pararajalingam Prasath , Meissner Barbara , Boyle Merrill , Davidson Jordan , Bushell Kevin R. , Lai Daniel , Farinha Pedro , Slack Graham W. , Morin Gregg B. , Shah Sohrab , Sen Dipankar , Jones Steven J. M. , Mungall Andrew J. , Gascoyne Randy D. , Audas Timothy E. , Unrau Peter , Marra Marco A. , Connors Joseph M. , Steidl Christian , Scott David W. , Morin Ryan D. 
Published: September 2018

AbstractDiffuse large B-cell lymphoma (DLBCL) is an aggressive cancer originating from mature B-cells. Prognosis is strongly associated with molecular subgroup, although the driver mutations that distinguish the two main subgroups remain poorly defined. Through an integrative analysis of whole genomes, exomes, and transcriptomes, we have uncovered genes and non-coding loci that are commonly mutated in DLBCL. Our analysis has identified novel cis-regulatory sites, and implicates recurrent mutations in the 3′ UTR of NFKBIZ as a novel mechanism of oncogene deregulation and NF-κB pathway activation in the activated B-cell (ABC) subgroup. Small amplifications associated with over-expression of FCGR2B (the Fcγ receptor protein IIB), primarily in the germinal centre B-cell (GCB) subgroup, correlate with poor patient outcomes suggestive of a novel oncogene. These results expand the list of subgroup driver mutations that may facilitate implementation of improved diagnostic assays and could offer new avenues for the development of targeted therapeutics.
Strong coupling and induced transparency at room temperature with single quantum dots and gap plasmons
Authors: Leng Haixu , Szychowski Brian , Daniel Marie-Christine , Pelton Matthew 
Published: September 2018

AbstractCoherent coupling between plasmons and transition dipole moments in emitters can lead to two distinct spectral effects: vacuum Rabi splitting at strong coupling strengths, and induced transparency (also known as Fano interference) at intermediate coupling strengths. Achieving either strong or intermediate coupling between a single emitter and a localized plasmon resonance has the potential to enable single-photon nonlinearities and other extreme light–matter interactions, at room temperature and on the nanometer scale. Both effects produce two peaks in the spectrum of scattering from the plasmon resonance, and can thus be confused if scattering measurements alone are performed. Here we report measurements of scattering and photoluminescence from individual coupled plasmon–emitter systems that consist of a single colloidal quantum dot in the gap between a gold nanoparticle and a silver film. The measurements unambiguously demonstrate weak coupling (the Purcell effect), intermediate coupling (Fano interference), and strong coupling (Rabi splitting) at room temperature.
Interface dominated cooperative nanoprecipitation in interstitial alloys
Authors: Wang Hongcai , Zhang Xie , Yan Dingshun , Somsen Christoph , Eggeler Gunther 
Published: September 2018

AbstractSteels belong to one of the best established materials, however, the mechanisms of various phase transformations down to the nano length scale are still not fully clear. In this work, high-resolution transmission electron microscopy is combined with atomistic simulations to study the nanoscale carbide precipitation in a Fe–Cr–C alloy. We identify a cooperative growth mechanism that connects host lattice reconstruction and interstitial segregation at the growing interface front, which leads to a preferential growth of cementite (Fe3C) nanoprecipitates along a particular direction. This insight significantly improves our understanding of the mechanisms of nanoscale precipitation in interstitial alloys, and paves the way for engineering nanostructures to enhance the mechanical performance of alloys.
Engineered mRNA-expressed antibodies prevent respiratory syncytial virus infection
Authors: Tiwari Pooja Munnilal , Vanover Daryll , Lindsay Kevin E. , Bawage Swapnil Subhash , Kirschman Jonathan L. , Bhosle Sushma , Lifland Aaron W. , Zurla Chiara , Santangelo Philip J. 
Published: September 2018

AbstractThe lung is a critical prophylaxis target for clinically important infectious agents, including human respiratory syncytial virus (RSV) and influenza. Here, we develop a modular, synthetic mRNA-based approach to express neutralizing antibodies directly in the lung via aerosol, to prevent RSV infections. First, we express palivizumab, which reduces RSV F copies by 90.8%. Second, we express engineered, membrane-anchored palivizumab, which prevents detectable infection in transfected cells, reducing in vitro titer and in vivo RSV F copies by 99.7% and 89.6%, respectively. Finally, we express an anchored or secreted high-affinity, anti-RSV F, camelid antibody (RSV aVHH and sVHH). We demonstrate that RSV aVHH, but not RSV sVHH, significantly inhibits RSV 7 days post transfection, and we show that RSV aVHH is present in the lung for at least 28 days. Overall, our data suggests that expressing membrane-anchored broadly neutralizing antibodies in the lungs could potentially be a promising pulmonary prophylaxis approach.
Identification and tunable optical coherent control of transition-metal spins in silicon carbide
Authors: Bosma Tom , Lof Gerrit J. J. , Gilardoni Carmem M. , Zwier Olger V. , Hendriks Freddie , Magnusson Björn , Ellison Alexandre , Gällström Andreas , Ivanov Ivan G. , Son N. T. , Havenith Remco W. A. , van der Wal Caspar H. 
Published: September 2018

AbstractColor centers in wide-bandgap semiconductors are attractive systems for quantum technologies since they can combine long-coherent electronic spin and bright optical properties. Several suitable centers have been identified, most famously the nitrogen-vacancy defect in diamond. However, integration in communication technology is hindered by the fact that their optical transitions lie outside telecom wavelength bands. Several transition-metal impurities in silicon carbide do emit at and near telecom wavelengths, but knowledge about their spin and optical properties is incomplete. We present all-optical identification and coherent control of molybdenum-impurity spins in silicon carbide with transitions at near-infrared wavelengths. Our results identify spin S = 1/2 for both the electronic ground and excited state, with highly anisotropic spin properties that we apply for implementing optical control of ground-state spin coherence. Our results show optical lifetimes of ~60 ns and inhomogeneous spin dephasing times of ~0.3 μs, establishing relevance for quantum spin-photon interfacing.
Universal, high-fidelity quantum gates based on superadiabatic, geometric phases on a solid-state spin-qubit at room temperature
Authors: Kleißler Felix , Lazariev Andrii , Arroyo-Camejo Silvia 
Published: September 2018

AbstractGeometric phases and holonomies are a promising resource for the realization of high-fidelity quantum operations in noisy devices, due to their intrinsic fault-tolerance against parametric noise. However, for a long time their practical use in quantum computing was limited to proof of principle demonstrations. This was partly due to the need for adiabatic time evolution or the requirement of complex, high-dimensional state spaces and a large number of driving field parameters to achieve universal quantum gates employing holonomies. In 2016 Liang et al. proposed universal, superadiabatic, geometric quantum gates exploiting transitionless quantum driving, thereby offering fast and universal quantum gate performance on a simple two-level system. Here, we report on the experimental implementation of a set of non-commuting single-qubit superadiabatic, geometric quantum gates on the electron spin of the nitrogen-vacancy center in diamond under ambient conditions. This provides a promising and powerful tool for large-scale quantum computing under realistic, noisy experimental conditions.
High Expression of EpCAM and Sox2 is a Positive Prognosticator of Clinical Outcome for Head and Neck Carcinoma
Authors: Baumeister Philipp , Hollmann Alessandra , Kitz Julia , Afthonidou Artemis , Simon Florian , Shakhtour Julius , Mack Brigitte , Kranz Gisela , Libl Darko , Leu Martin , Schirmer Markus A. , Canis Martin , Belka Claus , Zitzelsberger Horst , Ganswindt Ute , Hess Julia , Jakob Mark , Unger Kristian , Gires Olivier 
Published: September 2018

AbstractLocally advanced head and neck squamous cell carcinomas (HNSCC) have limited prognosis due to frequent treatment failure. Currently, TNM-classification and human papillomavirus (HPV) infection are the sole clinical prognosticators of outcome. Tumor heterogeneity and stemness based on epithelial-mesenchymal-transition reportedly associate with therapy resistance. The capacity of epithelial marker EpCAM (EpEX), stemness regulator Sox2 and mesenchymal marker vimentin to predict clinical outcome of HSNCC patients was assessed upon immunohistochemistry staining in two cohorts of HNSCC patients treated with surgery and adjuvant radio (chemo) therapy (n = 94) and primary radio (chemo) therapy (n = 94), respectively. Prognostic values with respect to overall, disease-free and disease-specific survival were assessed in uni- and multivariate cox proportional hazard models to generate integrated risk scores. EpEX, Sox2 and vimentin displayed substantial inter- and intratumoral heterogeneity. EpEXhighand Sox2highpredicted improved clinical outcome in the discovery cohort and in the HPV-negative sub-cohort. EpEXhighand Sox2highwere confirmed as prognosticators of clinical outcome in the validation cohort treated with definitive radio(chemo)therapy. Importantly, EpEXhighidentified patients with improved survival within the HPV-negative subgroup of the validation cohort. Hence, Sox2highand particularly EpEXhighhave potential as tools to predict clinical performance of HNSCC patients, foremost HPV-negative cases, in the frame of molecular-guided treatment decision-making.
Chromosome 4q25 Variant rs6817105 Bring Sinus Node Dysfunction and Left Atrial Enlargement
Authors: Tomomori Shunsuke , Nakano Yukiko , Ochi Hidenori , Onohara Yuko , Sairaku Akinori , Tokuyama Takehito , Motoda Chikaaki , Matsumura Hiroya , Amioka Michitaka , Hironobe Naoya , Okubo Yousaku , Okamura Shou , Kawazoe Hiroshi , Nishiyama Yukie , Tahara Hidetoshi , Chayama Kazuaki , Kihara Yasuki 
Published: September 2018

AbstractGenome-wide association studies have reported a strong association of the single nucleotide polymorphism (SNP) rs6817105 (T > C) on chromosome 4q25 with atrial fibrillation (AF), but phenotype alterations conferred by this SNP have not been described. We genotyped SNP rs6817105 and examined the relationships among rs6817105 genotype, clinical characteristics, echocardiographic parameters, and electrophysiological parameters in 574 AF patients and 1,554 non-AF controls. Further, multiple microRNAs (miRNAs) are reported to be involved in atrial remodeling and AF pathogenesis, so we investigated relationships between rs6817105 genotype and serum concentrations of 2555 miRNAs. The rs6817105 minor allele frequency was significantly higher in AF patients than non-AF controls (66% vs. 47%, odds ratio 2.12, p = 4.9 × 10−26). Corrected sinus node recovery time (CSRT) was longer and left atrial volume index (LAVI) was larger in AF patients with the rs6817105 minor allele than patient non-carriers (CSRT: CC 557 ± 315 ms, CT 486 ± 273 ms, TT 447 ± 234 ms, p = 0.001; LAVI: CC 43.6 ± 12.1, CT 42.4 ± 13.6, TT 39.8 ± 11.6, p = 0.030). There were no significant differences between rs6817105 genotype and the serum concentrations of miRNAs. These findings strongly implicate rs6817105 minor allele in sinus node dysfunction and left atrial enlargement.
The genetics of university success
Authors: Smith-Woolley Emily , Ayorech Ziada , Dale Philip S. , von Stumm Sophie , Plomin Robert 
Published: September 2018

AbstractUniversity success, which includes enrolment in and achievement at university, as well as quality of the university, have all been linked to later earnings, health and wellbeing. However, little is known about the causes and correlates of differences in university-level outcomes. Capitalizing on both quantitative and molecular genetic data, we perform the first genetically sensitive investigation of university success with a UK-representative sample of 3,000 genotyped individuals and 3,000 twin pairs. Twin analyses indicate substantial additive genetic influence on university entrance exam achievement (57%), university enrolment (51%), university quality (57%) and university achievement (46%). We find that environmental effects tend to be non-shared, although the shared environment is substantial for university enrolment. Furthermore, using multivariate twin analysis, we show moderate to high genetic correlations between university success variables (0.27–0.76). Analyses using DNA alone also support genetic influence on university success. Indeed, a genome-wide polygenic score, derived from a 2016 genome-wide association study of years of education, predicts up to 5% of the variance in each university success variable. These findings suggest young adults select and modify their educational experiences in part based on their genetic propensities and highlight the potential for DNA-based predictions of real-world outcomes, which will continue to increase in predictive power.
Damping of selectively bonded 3D woven lattice materials
Authors: Salari-Sharif Ladan , Ryan Stephen M. , Pelacci Manuel , Guest James K. , Valdevit Lorenzo , Szyniszewski Stefan 
Published: September 2018

AbstractThe objective of this paper is to unveil a novel damping mechanism exhibited by 3D woven lattice materials (3DW), with emphasis on response to high-frequency excitations. Conventional bulk damping materials, such as rubber, exhibit relatively low stiffness, while stiff metals and ceramics typically have negligible damping. Here we demonstrate that high damping and structural stiffness can be simultaneously achieved in 3D woven lattice materials by brazing only select lattice joints, resulting in a load-bearing lattice frame intertwined with free, ‘floating’ lattice members to generate damping. The produced material samples are comparable to polymers in terms of damping coefficient, but are porous and have much higher maximum use temperature. We shed light on a novel damping mechanism enabled by an interplay between the forcing frequency imposed onto a load-bearing lattice frame and the motion of the embedded, free-moving lattice members. This novel class of damping metamaterials has potential use in a broad range of weight sensitive applications that require vibration attenuation at high frequencies.