bluuebunny/crossref_metadata_2025_split huggingface dataset:
Causal mechanisms and balancing selection inferred from genetic associations with polycystic ovary syndrome
Authors: Day Felix R. , Hinds David A. , Tung Joyce Y. , Stolk Lisette , Styrkarsdottir Unnur , Saxena Richa , Bjonnes Andrew , Broer Linda , Dunger David B. , Halldorsson Bjarni V. , Lawlor Debbie A. , Laval Guillaume , Mathieson Iain , McCardle Wendy L. , Louwers Yvonne , Meun Cindy , Ring Susan , Scott Robert A. , Sulem Patrick , Uitterlinden André G. , Wareham Nicholas J. , Thorsteinsdottir Unnur , Welt Corrine , Stefansson Kari , Laven Joop S. E. , Ong Ken K. , Perry John R. B. 
Published: September 2015

AbstractPolycystic ovary syndrome (PCOS) is the most common reproductive disorder in women, yet there is little consensus regarding its aetiology. Here we perform a genome-wide association study of PCOS in up to 5,184 self-reported cases of White European ancestry and 82,759 controls, with follow-up in a further ∼2,000 clinically validated cases and ∼100,000 controls. We identify six signals for PCOS at genome-wide statistical significance (P<5 × 10−8), in/near genes ERBB4/HER4, YAP1, THADA, FSHB, RAD50 and KRR1. Variants in/near three of the four epidermal growth factor receptor genes (ERBB2/HER2, ERBB3/HER3 and ERBB4/HER4) are associated with PCOS at or near genome-wide significance. Mendelian randomization analyses indicate causal roles in PCOS aetiology for higher BMI (P=2.5 × 10−9), higher insulin resistance (P=6 × 10−4) and lower serum sex hormone binding globulin concentrations (P=5 × 10−4). Furthermore, genetic susceptibility to later menopause is associated with higher PCOS risk (P=1.6 × 10−8) and PCOS-susceptibility alleles are associated with higher serum anti-Müllerian hormone concentrations in girls (P=8.9 × 10−5). This large-scale study implicates an aetiological role of the epidermal growth factor receptors, infers causal mechanisms relevant to clinical management and prevention, and suggests balancing selection mechanisms involved in PCOS risk.
Genomic analyses reveal recurrent mutations in epigenetic modifiers and the JAK–STAT pathway in Sézary syndrome
Authors: Kiel Mark J. , Sahasrabuddhe Anagh A. , Rolland Delphine C. M. , Velusamy Thirunavukkarasu , Chung Fuzon , Schaller Matthew , Bailey Nathanael G. , Betz Bryan L. , Miranda Roberto N. , Porcu Pierluigi , Byrd John C. , Medeiros L. Jeffrey , Kunkel Steven L. , Bahler David W. , Lim Megan S. , Elenitoba-Johnson Kojo S. J. 
Published: September 2015

AbstractSézary syndrome (SS) is an aggressive leukaemia of mature T cells with poor prognosis and limited options for targeted therapies. The comprehensive genetic alterations underlying the pathogenesis of SS are unknown. Here we integrate whole-genome sequencing (n=6), whole-exome sequencing (n=66) and array comparative genomic hybridization-based copy-number analysis (n=80) of primary SS samples. We identify previously unknown recurrent loss-of-function aberrations targeting members of the chromatin remodelling/histone modification and trithorax families, including ARID1A in which functional loss from nonsense and frameshift mutations and/or targeted deletions is observed in 40.3% of SS genomes. We also identify recurrent gain-of-function mutations targeting PLCG1 (9%) and JAK1, JAK3, STAT3 and STAT5B (JAK/STAT total ∼11%). Functional studies reveal sensitivity of JAK1-mutated primary SS cells to JAK inhibitor treatment. These results highlight the complex genomic landscape of SS and a role for inhibition of JAK/STAT pathways for the treatment of SS.
A database to enable discovery and design of piezoelectric materials
Authors: de Jong Maarten , Chen Wei , Geerlings Henry , Asta Mark , Persson Kristin Aslaug 
Published: September 2015

AbstractPiezoelectric materials are used in numerous applications requiring a coupling between electrical fields and mechanical strain. Despite the technological importance of this class of materials, for only a small fraction of all inorganic compounds which display compatible crystallographic symmetry, has piezoelectricity been characterized experimentally or computationally. In this work we employ first-principles calculations based on density functional perturbation theory to compute the piezoelectric tensors for nearly a thousand compounds, thereby increasing the available data for this property by more than an order of magnitude. The results are compared to select experimental data to establish the accuracy of the calculated properties. The details of the calculations are also presented, along with a description of the format of the database developed to make these computational results publicly available. In addition, the ways in which the database can be accessed and applied in materials development efforts are described.
Downregulating p22phox ameliorates inflammatory response in Angiotensin II-induced oxidative stress by regulating MAPK and NF-κB pathways in ARPE-19 cells
Authors: Qiu Yiguo , Tao Lifei , Lei Chunyan , Wang Jiaming , Yang Peizeng , Li Qiuhong , Lei Bo 
Published: September 2015

AbstractOxidative stress and inflammation are two interrelated biological events implicated in the pathogenesis of many diseases. Reactive oxygen species (ROS) produced under oxidative stress play a key role in pathological conditions. Inhibition of p22phox, an indispensable component of the NADPH oxidase (NOX) complex comprising the main source of ROS, plays a protective role in many ocular conditions by inhibiting the activation of NOXs and the generation of ROS. However, little is understood regarding the role of p22phox in oxidative stress-related inflammation in the eye. We used a p22phox small interfering RNA (siRNA) to transfect the retinal pigment epithelium (RPE)-derived cell line ARPE-19 and human primary RPE (hRPE) cells, then stimulated with Ang II. We observed a potent anti-inflammatory effect and studied the underlying mechanism. Downregulating p22phox resulted in decreased ROS generation, a reduction of NOXs (NOX1, 2, 4) and a decrease in inflammatory cytokine. In addition, p22phox downregulation reduced the activation of the MAPK and NF-κB signaling pathways. We conclude that inhibition of p22phox has an anti-inflammatory effect in Ang II-induced oxidative stress. Suppressing the MAPK and NF-κB pathways is involved in this protective effect. These results suggest that p22phox may provide a promising therapeutic target for oxidative stress-induced ocular inflammation
Tuning all-Optical Analog to Electromagnetically Induced Transparency in nanobeam cavities using nanoelectromechanical system
Authors: Shi Peng , Zhou Guangya , deng Jie , Tian Feng , Chau Fook Siong 
Published: September 2015

AbstractWe report the observations of all-optical electromagnetically induced transparency in nanostructures using waveguide side-coupled with photonic crystal nanobeam cavities, which has measured linewidths much narrower than individual resonances. The quality factor of transparency resonance can be 30 times larger than those of measured individual resonances. When the gap between cavity and waveguide is reduced to 10 nm, the bandwidth of destructive interference region can reach 10 nm while the width of transparency resonance is 0.3 nm. Subsequently, a comb-drive actuator is introduced to tune the line shape of the transparency resonance. The width of the peak is reduced to 15 pm and the resulting quality factor exceeds 105.
Differential Plasma-cell evolution is linked with Dermatophagoides pteronyssinus immunotherapy response
Authors: Fernández Tahia D. , Gómez Enrique , Doña Inmaculada , Campo Paloma , Rondon Carmen , Gonzalez Miguel , Gomez Francisca , Palomares Francisca , Salas Maria , Blanca Miguel , Mayorga Cristobalina , Torres Maria J. 
Published: September 2015

AbstractAllergic rhinitis is highly prevalent worldwide. Immunotherapy has been shown to control its symptoms, however, up to 30% of patients may not respond. Previous studies of the immunological mechanisms involved in allergen-immunotherapy (AIT) have focused on the humoral and T-cell response and several studies have evaluated some B-cell subpopulations during AIT and their role in immunological tolerance. However, although B and plasma-cell subpopulations are two of the most important cellular subtypes involved in allergic reactions, their relation with AIT efficacy remains unelucidated. The objective was to analyze the effects of immunotherapy on different B and plasma-cell subpopulations and whether these changes correlate with the clinical response to the treatment. Although no changes are found in B-cell subpopulations, responder patients show increased levels of memory B-cells even before the beginning of treatment. Changes in plasma-cell subpopulations are found, mainly in circulating inflammatory plasma-cells that could affect the response to the allergen. Moreover, an early increase of specific-IgG4 and IgG4 secreting-cells was found. All these suggest that the determination of the memory B-cells before the initiation of the treatment and the quantification of IgG4 and IgG4-secreting-cells in the first months of immunotherapy, could serve as markers for the clinical response to treatment.
Direct Observation of Long Electron-Hole Diffusion Distance in CH3NH3PbI3 Perovskite Thin Film
Authors: Li Yu , Yan Weibo , Li Yunlong , Wang Shufeng , Wang Wei , Bian Zuqiang , Xiao Lixin , Gong Qihuang 
Published: September 2015

AbstractIn high performance perovskite based solar cells, CH3NH3PbI3 is the key material. We carried out a study on charge diffusion in spin-coated CH3NH3PbI3 perovskite thin film by transient fluorescent spectroscopy. A thickness-dependent fluorescent lifetime was found. By coating the film with an electron or hole transfer layer, [6,6]-phenyl-C61-butyric acid methyl ester (PCBM) or 2,2′,7,7′-tetrakis(N,N-di-p-methoxyphenylamine)-9,9′-spirobifluorene (Spiro-OMeTAD) respectively, we observed the charge transfer directly through the fluorescence quenching. One-dimensional diffusion model was applied to obtain long charge diffusion distances in thick films, which is ~1.7 μm for electrons and up to ~6.3 μm for holes. Short diffusion distance of few hundreds of nanometer was also observed in thin film. This thickness dependent charge diffusion explained the formerly reported short charge diffusion distance (~100 nm) in films and resolved its confliction to thick working layer (300–500 nm) in real devices. This study presents direct support to the high performance perovskite solar cells and will benefit the devices’ design.
Oxidative Etching of Hexagonal Boron Nitride Toward Nanosheets with Defined Edges and Holes
Authors: Liao Yunlong , Tu Kaixiong , Han Xiaogang , Hu Liangbing , Connell John W. , Chen Zhongfang , Lin Yi 
Published: September 2015

AbstractLateral surface etching of two-dimensional (2D) nanosheets results in holey 2D nanosheets that have abundant edge atoms. Recent reports on holey graphene showed that holey 2D nanosheets can outperform their intact counterparts in many potential applications such as energy storage, catalysis, sensing, transistors and molecular transport/separation. From both fundamental and application perspectives, it is desirable to obtain holey 2D nanosheets with defined hole morphology and hole edge structures. This remains a great challenge for graphene and is little explored for other 2D nanomaterials. Here, a facile, controllable and scalable method is reported to carve geometrically defined pit/hole shapes and edges on hexagonal boron nitride (h-BN) basal plane surfaces via oxidative etching in air using silver nanoparticles as catalysts. The etched h-BN was further purified and exfoliated into nanosheets that inherited the hole/edge structural motifs and, under certain conditions, possess altered optical bandgap properties likely induced by the enriched zigzag edge atoms. This method opens up an exciting approach to further explore the physical and chemical properties of hole- and edge-enriched boron nitride and other 2D nanosheets, paving the way toward applications that can take advantage of their unique structures and performance characteristics.
Preimplantation death of xenomitochondrial mouse embryo harbouring bovine mitochondria
Authors: Kawahara Manabu , Koyama Shiori , Iimura Satomi , Yamazaki Wataru , Tanaka Aiko , Kohri Nanami , Sasaki Keisuke , Takahashi Masashi 
Published: September 2015

AbstractMitochondria, cellular organelles playing essential roles in eukaryotic cell metabolism, are thought to have evolved from bacteria. The organization of mtDNA is remarkably uniform across species, reflecting its vital and conserved role in oxidative phosphorylation (OXPHOS). Our objectives were to evaluate the compatibility of xenogeneic mitochondria in the development of preimplantation embryos in mammals. Mouse embryos harbouring bovine mitochondria (mtB-M embryos) were prepared by the cell-fusion technique employing the haemagglutinating virus of Japan (HVJ). The mtB-M embryos showed developmental delay at embryonic days (E) 3.5 after insemination. Furthermore, none of the mtB-M embryos could implant into the maternal uterus after embryo transfer, whereas control mouse embryos into which mitochondria from another mouse had been transferred developed as well as did non-manipulated embryos. When we performed quantitative PCR (qPCR) of mouse and bovine ND5, we found that the mtB-M embryos contained 8.3% of bovine mitochondria at the blastocyst stage. Thus, contamination with mitochondria from another species induces embryonic lethality prior to implantation into the maternal uterus. The heteroplasmic state of these xenogeneic mitochondria could have detrimental effects on preimplantation development, leading to preservation of species-specific mitochondrial integrity in mammals.
Synergy of multi-scale toughening and protective mechanisms at hierarchical branch-stem interfaces
Authors: Müller Ulrich , Gindl-Altmutter Wolfgang , Konnerth Johannes , Maier Günther A. , Keckes Jozef 
Published: September 2015

AbstractBiological materials possess a variety of artful interfaces whose size and properties are adapted to their hierarchical levels and functional requirements. Bone, nacre and wood exhibit an impressive fracture resistance based mainly on small crystallite size, interface organic adhesives and hierarchical microstructure. Currently, little is known about mechanical concepts in macroscopic biological interfaces like the branch-stem junction with estimated 1014 instances on earth and sizes up to few meters. Here we demonstrate that the crack growth in the upper region of the branch-stem interface of conifer trees proceeds along a narrow predefined region of transversally loaded tracheids, denoted as sacrificial tissue, which fail upon critical bending moments on the branch. The specific arrangement of the tracheids allows disconnecting the overloaded branch from the stem in a controlled way by maintaining the stem integrity. The interface microstructure based on the sharply adjusted cell orientation and cell helical angle secures a zig-zag crack propagation path, mechanical interlock closing after the bending moment is removed, crack gap bridging and self-repairing by resin deposition. The multi-scale synergetic concepts allows for a controllable crack growth between stiff stem and flexible branch, as well as mechanical tree integrity, intact physiological functions and recovery after the cracking.
A new nanocomposite forward osmosis membrane custom-designed for treating shale gas wastewater
Authors: Qin Detao , Liu Zhaoyang , Delai Sun Darren , Song Xiaoxiao , Bai Hongwei 
Published: September 2015

AbstractManaging the wastewater discharged from oil and shale gas fields is a big challenge, because this kind of wastewater is normally polluted by high contents of both oils and salts. Conventional pressure-driven membranes experience little success for treating this wastewater because of either severe membrane fouling or incapability of desalination. In this study, we designed a new nanocomposite forward osmosis (FO) membrane for accomplishing simultaneous oil/water separation and desalination. This nanocomposite FO membrane is composed of an oil-repelling and salt-rejecting hydrogel selective layer on top of a graphene oxide (GO) nanosheets infused polymeric support layer. The hydrogel selective layer demonstrates strong underwater oleophobicity that leads to superior anti-fouling capability under various oil/water emulsions and the infused GO in support layer can significantly mitigate internal concentration polarization (ICP) through reducing FO membrane structural parameter by as much as 20%. Compared with commercial FO membrane, this new FO membrane demonstrates more than three times higher water flux, higher removals for oil and salts (>99.9% for oil and >99.7% for multivalent ions) and significantly lower fouling tendency when investigated with simulated shale gas wastewater. These combined merits will endorse this new FO membrane with wide applications in treating highly saline and oily wastewaters.
Identification of an iridium(III) complex with anti-bacterial and anti-cancer activity
Authors: Lu Lihua , Liu Li-Juan , Chao Wei-chieh , Zhong Hai-Jing , Wang Modi , Chen Xiu-Ping , Lu Jin-Jian , Li Ruei-nian , Ma Dik-Lung , Leung Chung-Hang 
Published: September 2015

AbstractGroup 9 transition metal complexes have been widely explored as therapeutic agents due to their unique geometry, their propensity to undergo ligand exchanges with biomolecules and their diverse steric and electronic properties. These metal complexes can offer distinct modes of action in living organisms compared to carbon-based molecules. In this study, we investigated the antimicrobial and anti-proliferative abilities of a series of cyclometallated iridium(III) complexes. The iridium(III) complex 1 inhibited the growth of S. aureus with MIC and MBC values of 3.60 and 7.19 μM, respectively, indicating its potent bactericidal activity. Moreover, complex 1 also exhibited cytotoxicity against a number of cancer cell lines, with particular potency against ovarian, cervical and melanoma cells. This cyclometallated iridium(III) complex is the first example of a substitutionally-inert, Group 9 organometallic compound utilized as a direct and selective inhibitor of S. aureus.
Inhibition of the Rho/Rho kinase pathway prevents lipopolysaccharide-induced hyperalgesia and the release of TNF-α and IL-1β in the mouse spinal cord
Authors: Wang Cunjin , Song Siyuan , Zhang Yang , Ge Yali , Fang Xiangzhi , Huang Tianfeng , Du Jin , Gao Ju 
Published: September 2015

AbstractAdministration of lipopolysaccharide (LPS) by various routes produces profound inflammatory pain hypersensitivity. However, the molecular events that induce this response remain largely uncharacterized. In the present study, we sought to elucidate the role of the Rho/Rho kinase (ROCK) pathway in the release of tumor necrosis factor-α (TNF-α) and interleukin 1β (IL-1β) following injection of LPS into the mouse paw, which is associated with nociceptive behavior. The spinal cord of LPS-treated mice showed increased active GTP-bound RhoA and upregulation of ROCK2 and c-fos compared to the normal saline group. Furthermore, the inflammation-related cytokines TNF-α and IL-1β were markedly increased in the spinal dorsal horn after intraplantar injection of LPS. However, the latter effects were prevented by prophylactic intrathecal administration of the Rho inhibitor (C3 exoenzyme) or the ROCK inhibitor (Y27632). Collectively, our results suggest that the Rho/ROCK signaling pathway plays a critical role in LPS-induced inflammatory pain and that this pathway is coincident with the release of the pro-nociceptive cytokines TNF-α and IL-1β, which produces hyperalgesia.
Local bacteria affect the efficacy of chemotherapeutic drugs
Authors: Lehouritis Panos , Cummins Joanne , Stanton Michael , Murphy Carola T. , McCarthy Florence O. , Reid Gregor , Urbaniak Camilla , Byrne William L. , Tangney Mark 
Published: September 2015

AbstractIn this study, the potential effects of bacteria on the efficacy of frequently used chemotherapies was examined. Bacteria and cancer cell lines were examined in vitro and in vivo for changes in the efficacy of cancer cell killing mediated by chemotherapeutic agents. Of 30 drugs examined in vitro, the efficacy of 10 was found to be significantly inhibited by certain bacteria, while the same bacteria improved the efficacy of six others. HPLC and mass spectrometry analyses of sample drugs (gemcitabine, fludarabine, cladribine, CB1954) demonstrated modification of drug chemical structure. The chemoresistance or increased cytotoxicity observed in vitro with sample drugs (gemcitabine and CB1954) was replicated in in vivo murine subcutaneous tumour models. These findings suggest that bacterial presence in the body due to systemic or local infection may influence tumour responses or off-target toxicity during chemotherapy.
The shadow of the future promotes cooperation in a repeated prisoner’s dilemma for children
Authors: Blake Peter R. , Rand David G. , Tingley Dustin , Warneken Felix 
Published: September 2015

AbstractCooperation among genetically unrelated individuals can be supported by direct reciprocity. Theoretical models and experiments with adults show that the possibility of future interactions with the same partner can promote cooperation via conditionally cooperative strategies such as tit-for-tat (TFT). Here, we introduce a novel implementation of the repeated Prisoner’s Dilemma (PD) designed for children to examine whether repeated interactions can successfully promote cooperation in 10 and 11 year olds. We find that children cooperate substantially more in repeated PDs than in one-shot PDs. We also find that girls cooperate more than boys and that children with more conduct problems cooperate less. Finally, we find that children use conditional cooperation strategies but that these strategies vary by gender and conduct problem rating. Specifically, girls and children with few conduct problems appear to follow an altruistic version of win-stay, lose-shift (WSLS), attempting to re-establish cooperation after they had defected. Boys and children with more conduct problems appear to follow a Grim strategy, defecting for the duration after the partner defects. Thus we provide evidence that children utilize the power of direct reciprocity to promote cooperation in strategic interactions and that, by late elementary school, distinct strategies of conditional cooperation have emerged.
Novel non-local effects in three-terminal hybrid devices with quantum dot
Authors: Michałek G. , Domański T. , Bułka B.R. , Wysokiński K.I. 
Published: September 2015

AbstractWe predict non-local effect in the three-terminal hybrid device consisting of the quantum dot (QD) tunnel coupled to two normal and one superconducting reservoirs. It manifests itself as the negative non-local resistance and results from the competition between the ballistic electron transfer (ET) and the crossed Andreev scattering (CAR). The effect is robust both in the linear and non-linear regimes. In the latter case the screening of charges and the long-range interactions play significant role. We show that sign change of the non-local conductance depends on the subgap Shiba/Andreev states and it takes place even in absence of the Coulomb interactions. The effect is large and can be experimentally verified using the four probe setup. Since the induced non-local voltage changes sign and magnitude upon varying the gate potential and/or coupling of the quantum dot to the superconducting lead, such measurement could hence provide a controlled and precise method to determine the positions of the Shiba/Andreev states. Our predictions ought to be contrasted with non-local effects observed hitherto in the three-terminal planar junctions where the residual negative non-local conductance has been observed at large voltages, related to the Thouless energy of quasiparticles tunneling through the superconducting slab.