bluuebunny/crossref_metadata_2025_split huggingface dataset:
Germline variation in ADAMTSL1 is associated with prognosis following breast cancer treatment in young women
Authors: Kadalayil Latha , Khan Sofia , Nevanlinna Heli , Fasching Peter A. , Couch Fergus J. , Hopper John L. , Liu Jianjun , Maishman Tom , Durcan Lorraine , Gerty Sue , Blomqvist Carl , Rack Brigitte , Janni Wolfgang , Collins Andrew , Eccles Diana , Tapper William 
Published: November 2017

AbstractTo identify genetic variants associated with breast cancer prognosis we conduct a meta-analysis of overall survival (OS) and disease-free survival (DFS) in 6042 patients from four cohorts. In young women, breast cancer is characterized by a higher incidence of adverse pathological features, unique gene expression profiles and worse survival, which may relate to germline variation. To explore this hypothesis, we also perform survival analysis in 2315 patients aged ≤ 40 years at diagnosis. Here, we identify two SNPs associated with early-onset DFS, rs715212 (Pmeta = 3.54 × 10−5) and rs10963755 (Pmeta = 3.91 × 10−4) in ADAMTSL1. The effect of these SNPs is independent of classical prognostic factors and there is no heterogeneity between cohorts. Most importantly, the association with rs715212 is noteworthy (FPRP <0.2) and approaches genome-wide significance in multivariable analysis (Pmultivariable = 5.37 × 10−8). Expression quantitative trait analysis provides tentative evidence that rs715212 may influence AREG expression (PeQTL = 0.035), although further functional studies are needed to confirm this association and determine a mechanism.
Female-specific myoinhibitory peptide neurons regulate mating receptivity in Drosophila melanogaster
Authors: Jang Yong-Hoon , Chae Hyo-Seok , Kim Young-Joon 
Published: November 2017

AbstractUpon mating, fruit fly females become refractory to further mating for several days. An ejaculate protein called sex peptide (SP) acts on uterine neurons to trigger this behavioural change, but it is still unclear how the SP signal modifies the mating decision. Here we describe two groups of female-specific local interneurons that are important for this process—the ventral abdominal lateral (vAL) and ventral abdominal medial (vAM) interneurons. Both vAL and vAM express myoinhibitory peptide (Mip)-GAL4. vAL is positive for Mip neuropeptides and the sex-determining transcriptional factor doublesex. Silencing the Mip neurons in females induces active rejection of male courtship attempts, whereas activation of the Mip neurons makes even mated females receptive to re-mating. vAL and vAM are located in the abdominal ganglion (AG) where they relay the SP signal to other AG neurons that project to the brain. Mip neuropeptides appear to promote mating receptivity both in virgins and mated females, although it is dispensable for normal mating in virgin females.
Anti-Stokes photoluminescence probing k-conservation and thermalization of minority carriers in degenerately doped semiconductors
Authors: Mergenthaler K. , Anttu N. , Vainorius N. , Aghaeipour M. , Lehmann S. , Borgström M. T. , Samuelson L. , Pistol M.-E. 
Published: November 2017

AbstractIt has recently been found that anti-Stokes photoluminescence can be observed in degenerately n-doped indium phosphide nanowires, when exciting directly into the electron gas. This anti-Stokes mechanism has not been observed before and allows the study of carrier relaxation and recombination using standard photoluminescence techniques. It is important to know if this anti-Stokes photoluminescence also occurs in bulk semiconductors as well as its relation to carrier recombination and relaxation. Here we show that similar anti-Stokes photoluminescence can indeed be observed in degenerately doped bulk indium phosphide and gallium arsenide and is caused by minority carriers scattering to high momenta by phonons. We find in addition that the radiative electron-hole recombination is highly momentum-conserving and that photogenerated minority carriers recombine before relaxing to the band edge at low temperatures. These observations challenge the use of models assuming thermalization of minority carriers in the analysis of highly doped devices.
Human eye-inspired soft optoelectronic device using high-density MoS2-graphene curved image sensor array
Authors: Choi Changsoon , Choi Moon Kee , Liu Siyi , Kim Minsung , Park Ok Kyu , Im Changkyun , Kim Jaemin , Qin Xiaoliang , Lee Gil Ju , Cho Kyoung Won , Kim Myungbin , Joh Eehyung , Lee Jongha , Son Donghee , Kwon Seung-Hae , Jeon Noo Li , Song Young Min , Lu Nanshu , Kim Dae-Hyeong 
Published: November 2017

AbstractSoft bioelectronic devices provide new opportunities for next-generation implantable devices owing to their soft mechanical nature that leads to minimal tissue damages and immune responses. However, a soft form of the implantable optoelectronic device for optical sensing and retinal stimulation has not been developed yet because of the bulkiness and rigidity of conventional imaging modules and their composing materials. Here, we describe a high-density and hemispherically curved image sensor array that leverages the atomically thin MoS2-graphene heterostructure and strain-releasing device designs. The hemispherically curved image sensor array exhibits infrared blindness and successfully acquires pixelated optical signals. We corroborate the validity of the proposed soft materials and ultrathin device designs through theoretical modeling and finite element analysis. Then, we propose the ultrathin hemispherically curved image sensor array as a promising imaging element in the soft retinal implant. The CurvIS array is applied as a human eye-inspired soft implantable optoelectronic device that can detect optical signals and apply programmed electrical stimulation to optic nerves with minimum mechanical side effects to the retina.
Microscale cavitation as a mechanism for nucleating earthquakes at the base of the seismogenic zone
Authors: Verberne Berend A. , Chen Jianye , Niemeijer André R. , de Bresser Johannes H. P. , Pennock Gillian M. , Drury Martyn R. , Spiers Christopher J. 
Published: November 2017

AbstractMajor earthquakes frequently nucleate near the base of the seismogenic zone, close to the brittle-ductile transition. Fault zone rupture at greater depths is inhibited by ductile flow of rock. However, the microphysical mechanisms responsible for the transition from ductile flow to seismogenic brittle/frictional behaviour at shallower depths remain unclear. Here we show that the flow-to-friction transition in experimentally simulated calcite faults is characterized by a transition from dislocation and diffusion creep to dilatant deformation, involving incompletely accommodated grain boundary sliding. With increasing shear rate or decreasing temperature, dislocation and diffusion creep become too slow to accommodate the imposed shear strain rate, leading to intergranular cavitation, weakening, strain localization, and a switch from stable flow to runaway fault rupture. The observed shear instability, triggered by the onset of microscale cavitation, provides a key mechanism for bringing about the brittle-ductile transition and for nucleating earthquakes at the base of the seismogenic zone.
MyD88 promotes myoblast fusion in a cell-autonomous manner
Authors: Hindi Sajedah M. , Shin Jonghyun , Gallot Yann S. , Straughn Alex R. , Simionescu-Bankston Adriana , Hindi Lubna , Xiong Guangyan , Friedland Robert P. , Kumar Ashok 
Published: November 2017

AbstractMyoblast fusion is an indispensable step for skeletal muscle development, postnatal growth, and regeneration. Myeloid differentiation primary response gene 88 (MyD88) is an adaptor protein that mediates Toll-like receptors and interleukin-1 receptor signaling. Here we report a cell-autonomous role of MyD88 in the regulation of myoblast fusion. MyD88 protein levels are increased during in vitro myogenesis and in conditions that promote skeletal muscle growth in vivo. Deletion of MyD88 impairs fusion of myoblasts without affecting their survival, proliferation, or differentiation. MyD88 regulates non-canonical NF-κB and canonical Wnt signaling during myogenesis and promotes skeletal muscle growth and overload-induced myofiber hypertrophy in mice. Ablation of MyD88 reduces myofiber size during muscle regeneration, whereas its overexpression promotes fusion of exogenous myoblasts to injured myofibers. Our study shows that MyD88 modulates myoblast fusion and suggests that augmenting its levels may be a therapeutic approach to improve skeletal muscle formation in degenerative muscle disorders.
Dynamically controlled Purcell enhancement of visible spontaneous emission in a gated plasmonic heterostructure
Authors: Lu Yu-Jung , Sokhoyan Ruzan , Cheng Wen-Hui , Kafaie Shirmanesh Ghazaleh , Davoyan Artur R. , Pala Ragip A. , Thyagarajan Krishnan , Atwater Harry A. 
Published: November 2017

AbstractEmission control of colloidal quantum dots (QDs) is a cornerstone of modern high-quality lighting and display technologies. Dynamic emission control of colloidal QDs in an optoelectronic device is usually achieved by changing the optical pump intensity or injection current density. Here we propose and demonstrate a distinctly different mechanism for the temporal modulation of QD emission intensity at constant optical pumping rate. Our mechanism is based on the electrically controlled modulation of the local density of optical states (LDOS) at the position of the QDs, resulting in the modulation of the QD spontaneous emission rate, far-field emission intensity, and quantum yield. We manipulate the LDOS via field effect-induced optical permittivity modulation of an ultrathin titanium nitride (TiN) film, which is incorporated in a gated TiN/SiO2/Ag plasmonic heterostructure. The demonstrated electrical control of the colloidal QD emission provides a new approach for modulating intensity of light in displays and other optoelectronics.
Universal model of individual and population mobility on diverse spatial scales
Authors: Yan Xiao-Yong , Wang Wen-Xu , Gao Zi-You , Lai Ying-Cheng 
Published: November 2017

AbstractStudies of human mobility in the past decade revealed a number of general scaling laws. However, to reproduce the scaling behaviors quantitatively at both the individual and population levels simultaneously remains to be an outstanding problem. Moreover, recent evidence suggests that spatial scales have a significant effect on human mobility, raising the need for formulating a universal model suited for human mobility at different levels and spatial scales. Here we develop a general model by combining memory effect and population-induced competition to enable accurate prediction of human mobility based on population distribution only. A variety of individual and collective mobility patterns such as scaling behaviors and trajectory motifs are accurately predicted for different countries and cities of diverse spatial scales. Our model establishes a universal underlying mechanism capable of explaining a variety of human mobility behaviors, and has significant applications for understanding many dynamical processes associated with human mobility.
Health benefits of late-onset metformin treatment every other week in mice
Authors: Alfaras Irene , Mitchell Sarah J. , Mora Hector , Lugo Darisbeth Rosario , Warren Alessandra , Navas-Enamorado Ignacio , Hoffmann Vickie , Hine Christopher , Mitchell James R. , Le Couteur David G. , Cogger Victoria C. , Bernier Michel , de Cabo Rafael 
Published: November 2017

AbstractChronic 1% metformin treatment is nephrotoxic in mice, but this dose may nonetheless confer health benefits if given intermittently rather than continuously. Here, we examined the effects of 1% metformin given every-other week (EOW) or two consecutive weeks per month (2WM) on survival of 2-year-old male mice fed standard chow. EOW and 2WM mice had comparable life span compared with control mice. A significant reduction in body weight within the first few weeks of metformin treatment was observed without impact on food consumption and energy expenditure. Moreover, there were differences in the action of metformin on metabolic markers between the EOW and 2WM groups, with EOW metformin conferring greater benefits. Age-associated kidney lesions became more pronounced with metformin, although without pathological consequences. In the liver, metformin treatment led to an overall reduction in steatosis and was accompanied by distinct transcriptomic and metabolomic signatures in response to EOW versus 2WM regimens. Thus, the absence of adverse outcomes associated with chronic, intermittent use of 1% metformin in old mice has clinical translatability into the biology of aging in humans.
Krüpple-like-factor 4 Attenuates Lung Fibrosis via Inhibiting Epithelial-mesenchymal Transition
Authors: Lin Lianjun , Han Qian , Xiong Yan , Li Ting , Liu Zhonghui , Xu Huiying , Wu Yanping , Wang Nanping , Liu Xinmin 
Published: November 2017

AbstractEpithelial-mesenchymal transition (EMT) plays an important role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Krüpple-like-factor 4 (KLF4), has been suggested to play an important role in the phenotype transition. However, its function in pulmonary fibrosis and EMT of human alveolar epithelial cells (AECs) remains unclear. This study aimed to examine the role of KLF4 in pulmonary fibrosis and EMT. Decreased expression of KLF4 was first observed in human IPF lung tissues and models of bleomycin-induced pulmonary fibrosis. Transgenic mice with overexpression of KLF4 were subjected to bleomycin-induced pulmonary fibrosis model and showed attenuated lung fibrosis and EMT compared to wild type group. Furthermore, the effects overexpression and knockdown of KLF4 on TGF-β1-induced EMT were examined in AECs. Adenovirus-mediated overexpression of KLF4 attenuated TGF-β1-induced EMT and activation of Smad2/3 and Dvl in AECs. Conversely, knockdown of KLF4 promoted the activation of pathways above mentioned and TGF-β1-induced EMT. Our results demonstrates that KLF4 plays an important role in bleomycin-induced lung fibrosis through suppressing TGFβ1-induced EMT. Thus, it may serve as a potential target for the treatment of pulmonary fibrosis.
miRDDCR: a miRNA-based method to comprehensively infer drug-disease causal relationships
Authors: Chen Hailin , Zhang Zuping , Peng Wei 
Published: November 2017

AbstractRevealing the cause-and-effect mechanism behind drug-disease relationships remains a challenging task. Recent studies suggested that drugs can target microRNAs (miRNAs) and alter their expression levels. In the meanwhile, the inappropriate expression of miRNAs will lead to various diseases. Therefore, targeting specific miRNAs by small-molecule drugs to modulate their activities provides a promising approach to human disease treatment. However, few studies attempt to discover drug-disease causal relationships through the molecular level of miRNAs. Here, we developed a miRNA-based inference method miRDDCR to comprehensively predict drug-disease causal relationships. We first constructed a three-layer drug-miRNA-disease heterogeneous network by combining similarity measurements, existing drug-miRNA associations and miRNA-disease associations. Then, we extended the algorithm of Random Walk to the three-layer heterogeneous network and ranked the potential indications for drugs. Leave-one-out cross-validations and case studies demonstrated that our method miRDDCR can achieve excellent prediction power. Compared with related methods, our causality discovery-based algorithm showed superior prediction ability and highlighted the molecular basis miRNAs, which can be used to assist in the experimental design for drug development and disease treatment. Finally, comprehensively inferred drug-disease causal relationships were released for further studies.
Pulse frequency dependency of photobiomodulation on the bioenergetic functions of human dental pulp stem cells
Authors: Kim Hong Bae , Baik Ku Youn , Choung Pill-Hoon , Chung Jong Hoon 
Published: November 2017

AbstractPhotobiomodulation (PBM) therapy contributes to pain relief, wound healing, and tissue regeneration. The pulsed wave (PW) mode has been reported to be more effective than the continuous wave (CW) mode when applying PBM to many biological systems. However, the reason for the higher effectiveness of PW-PBM is poorly understood. Herein, we suggest using delayed luminescence (DL) as a reporter of mitochondrial activity after PBM treatment. DL originates mainly from mitochondrial electron transport chain systems, which produce reactive oxygen species (ROS) and adenosine triphosphate (ATP). The decay time of DL depends on the pulse frequencies of applied light, which correlate with the biological responses of human dental pulp stem cells (hDPSCs). Using a low-power light whose wavelength is 810 nm and energy density is 38 mJ/cm2, we find that a 300-Hz pulse frequency prolonged the DL pattern and enhanced alkaline phosphatase activity. In addition, we analyze mitochondrial morphological changes and their volume density and find evidence supporting mitochondrial physiological changes from PBM treatment. Our data suggest a new methodology for determining the effectiveness of PBM and the specific pulse frequency dependency of PBM in the differentiation of hDPSCs.
Allometric scaling of skin thickness, elasticity, viscoelasticity to mass for micro-medical device translation: from mice, rats, rabbits, pigs to humans
Authors: Wei Jonathan C. J. , Edwards Grant A. , Martin Darren J. , Huang Han , Crichton Michael L. , Kendall Mark A. F. 
Published: November 2017

AbstractEmerging micro-scale medical devices are showing promise, whether in delivering drugs or extracting diagnostic biomarkers from skin. In progressing these devices through animal models towards clinical products, understanding the mechanical properties and skin tissue structure with which they interact will be important. Here, through measurement and analytical modelling, we advanced knowledge of these properties for commonly used laboratory animals and humans (~30 g to ~150 kg). We hypothesised that skin’s stiffness is a function of the thickness of its layers through allometric scaling, which could be estimated from knowing a species’ body mass. Results suggest that skin layer thicknesses are proportional to body mass with similar composition ratios, inter- and intra-species. Experimental trends showed elastic moduli increased with body mass, except for human skin. To interpret the relationship between species, we developed a simple analytical model for the bulk elastic moduli of skin, which correlated well with experimental data. Our model suggest that layer thicknesses may be a key driver of structural stiffness, as the skin layer constituents are physically and therefore mechanically similar between species. Our findings help advance the knowledge of mammalian skin mechanical properties, providing a route towards streamlined micro-device research and development onto clinical use.
An Evolutionary Game Theory Model of Spontaneous Brain Functioning
Authors: Madeo Dario , Talarico Agostino , Pascual-Leone Alvaro , Mocenni Chiara , Santarnecchi Emiliano 
Published: November 2017

AbstractOur brain is a complex system of interconnected regions spontaneously organized into distinct networks. The integration of information between and within these networks is a continuous process that can be observed even when the brain is at rest, i.e. not engaged in any particular task. Moreover, such spontaneous dynamics show predictive value over individual cognitive profile and constitute a potential marker in neurological and psychiatric conditions, making its understanding of fundamental importance in modern neuroscience. Here we present a theoretical and mathematical model based on an extension of evolutionary game theory on networks (EGN), able to capture brain's interregional dynamics by balancing emulative and non-emulative attitudes among brain regions. This results in the net behavior of nodes composing resting-state networks identified using functional magnetic resonance imaging (fMRI), determining their moment-to-moment level of activation and inhibition as expressed by positive and negative shifts in BOLD fMRI signal. By spontaneously generating low-frequency oscillatory behaviors, the EGN model is able to mimic functional connectivity dynamics, approximate fMRI time series on the basis of initial subset of available data, as well as simulate the impact of network lesions and provide evidence of compensation mechanisms across networks. Results suggest evolutionary game theory on networks as a new potential framework for the understanding of human brain network dynamics.
The corepressor NCOR1 regulates the survival of single-positive thymocytes
Authors: Müller Lena , Hainberger Daniela , Stolz Valentina , Hamminger Patricia , Hassan Hammad , Preglej Teresa , Boucheron Nicole , Sakaguchi Shinya , Wiegers G. Jan , Villunger Andreas , Auwerx Johan , Ellmeier Wilfried 
Published: November 2017

AbstractNuclear receptor corepressor 1 (NCOR1) is a transcriptional regulator bridging repressive chromatin modifying enzymes with transcription factors. NCOR1 regulates many biological processes, however its role in T cells is not known. Here we show thatCd4-Cre-mediated deletion of NCOR1 (NCOR1 cKOCd4) resulted in a reduction of peripheral T cell numbers due to a decrease in single-positive (SP) thymocytes. In contrast, double-positive (DP) thymocyte numbers were not affected in the absence of NCOR1. The reduction in SP cells was due to diminished survival of NCOR1-null postselection TCRβhiCD69+and mature TCRβhiCD69−thymocytes. NCOR1-null thymocytes expressed elevated levels of the pro-apoptotic factor BIM and showed a higher fraction of cleaved caspase 3-positive cells upon TCR stimulationex vivo. However, staphylococcal enterotoxin B (SEB)-mediated deletion of Vβ8+CD4SP thymocytes was normal, suggesting that negative selection is not altered in the absence of NCOR1. Finally, transgenic expression of the pro-survival protein BCL2 restored the population of CD69+thymocytes in NCOR1 cKOCd4mice to a similar percentage as observed in WT mice. Together, these data identify NCOR1 as a crucial regulator of the survival of SP thymocytes and revealed that NCOR1 is essential for the proper generation of the peripheral T cell pool.
Three Dimensional Honeycomb Patterned Fibrinogen Based Nanofibers Induce Substantial Osteogenic Response of Mesenchymal Stem Cells
Authors: Nedjari Salima , Awaja Firas , Altankov George 
Published: November 2017

AbstractStem cells therapy offers a viable alternative for treatment of bone disorders to the conventional bone grafting. However clinical therapies are still hindered by the insufficient knowledge on the conditions that maximize stem cells differentiation. Hereby, we introduce a novel 3D honeycomb architecture scaffold that strongly support osteogenic differentiation of human adipose derived mesenchymal stem cells (ADMSCs). The scaffold is based on electrospun hybrid nanofibers consisting of poly (L-lactide ε-caprolactone) and fibrinogen (PLCL/FBG). Classical fibers orientations, random or aligned were also produced and studied for comparison. The overall morphology of ADMSC’s generally followed the nanofibers orientation and dimensionality developing regular focal adhesions and direction-dependent actin cytoskeleton bundles. However, there was an initial tendency for cells rounding on honeycomb scaffolds before ADMSCs formed a distinct bridging network. This specific cells organization appeared to have significant impact on the differentiation potential of ADMSCs towards osteogenic lineage, as indicated by the alkaline phosphatase production, calcium deposition and specific genes expression. Collectively, it was observed synergistic effect of nanofibers with honeycomb architecture on the behavior of ADMSCs entering osteogenic path of differentiation which outlines the potential benefits from insertion of such bioinspired geometrical cues within scaffolds for bone tissue engineering.