bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interplay between Notch1 and Notch3 promotes EMT and tumor initiation in squamous cell carcinoma
Authors: Natsuizaka Mitsuteru , Whelan Kelly A. , Kagawa Shingo , Tanaka Koji , Giroux Veronique , Chandramouleeswaran Prasanna M. , Long Apple , Sahu Varun , Darling Douglas S. , Que Jianwen , Yang Yizeng , Katz Jonathan P. , Wileyto E. Paul , Basu Devraj , Kita Yoshiaki , Natsugoe Shoji , Naganuma Seiji , Klein-Szanto Andres J. , Diehl J. Alan , Bass Adam J. , Wong Kwok-Kin , Rustgi Anil K. , Nakagawa Hiroshi 
Published: November 2017

AbstractNotch1 transactivates Notch3 to drive terminal differentiation in stratified squamous epithelia. Notch1 and other Notch receptor paralogs cooperate to act as a tumor suppressor in squamous cell carcinomas (SCCs). However, Notch1 can be stochastically activated to promote carcinogenesis in murine models of SCC. Activated form of Notch1 promotes xenograft tumor growth when expressed ectopically. Here, we demonstrate that Notch1 activation and epithelial–mesenchymal transition (EMT) are coupled to promote SCC tumor initiation in concert with transforming growth factor (TGF)-β present in the tumor microenvironment. We find that TGFβ activates the transcription factor ZEB1 to repress Notch3, thereby limiting terminal differentiation. Concurrently, TGFβ drives Notch1-mediated EMT to generate tumor initiating cells characterized by high CD44 expression. Moreover, Notch1 is activated in a small subset of SCC cells at the invasive tumor front and predicts for poor prognosis of esophageal SCC, shedding light upon the tumor promoting oncogenic aspect of Notch1 in SCC.
Antagonistic bacteria disrupt calcium homeostasis and immobilize algal cells
Authors: Aiyar Prasad , Schaeme Daniel , García-Altares María , Carrasco Flores David , Dathe Hannes , Hertweck Christian , Sasso Severin , Mittag Maria 
Published: November 2017

AbstractPhotosynthetic unicellular organisms, known as microalgae, are key contributors to carbon fixation on Earth. Their biotic interactions with other microbes shape aquatic microbial communities and influence the global photosynthetic capacity. So far, limited information is available on molecular factors that govern these interactions. We show that the bacterium Pseudomonas protegens strongly inhibits the growth and alters the morphology of the biflagellated green alga Chlamydomonas reinhardtii. This antagonistic effect is decreased in a bacterial mutant lacking orfamides, demonstrating that these secreted cyclic lipopeptides play an important role in the algal–bacterial interaction. Using an aequorin Ca2+-reporter assay, we show that orfamide A triggers an increase in cytosolic Ca2+ in C. reinhardtii and causes deflagellation of algal cells. These effects of orfamide A, which are specific to the algal class of Chlorophyceae and appear to target a Ca2+ channel in the plasma membrane, represent a novel biological activity for cyclic lipopeptides.
GABAA receptor dependent synaptic inhibition rapidly tunes KCC2 activity via the Cl−-sensitive WNK1 kinase
Authors: Heubl Martin , Zhang Jinwei , Pressey Jessica C. , Al Awabdh Sana , Renner Marianne , Gomez-Castro Ferran , Moutkine Imane , Eugène Emmanuel , Russeau Marion , Kahle Kristopher T. , Poncer Jean Christophe , Lévi Sabine 
Published: November 2017

AbstractThe K+–Cl−co-transporter KCC2 (SLC12A5) tunes the efficacy of GABAAreceptor-mediated transmission by regulating the intraneuronal chloride concentration [Cl−]i. KCC2 undergoes activity-dependent regulation in both physiological and pathological conditions. The regulation of KCC2 by synaptic excitation is well documented; however, whether the transporter is regulated by synaptic inhibition is unknown. Here we report a mechanism of KCC2 regulation by GABAAreceptor (GABAAR)-mediated transmission in mature hippocampal neurons. Enhancing GABAAR-mediated inhibition confines KCC2 to the plasma membrane, while antagonizing inhibition reduces KCC2 surface expression by increasing the lateral diffusion and endocytosis of the transporter. This mechanism utilizes Cl−as an intracellular secondary messenger and is dependent on phosphorylation of KCC2 at threonines 906 and 1007 by the Cl−-sensing kinase WNK1. We propose this mechanism contributes to the homeostasis of synaptic inhibition by rapidly adjusting neuronal [Cl−]ito GABAAR activity.
Microneedle-array patches loaded with dual mineralized protein/peptide particles for type 2 diabetes therapy
Authors: Chen Wei , Tian Rui , Xu Can , Yung Bryant C. , Wang Guohao , Liu Yijing , Ni Qianqian , Zhang Fuwu , Zhou Zijian , Wang Jingjing , Niu Gang , Ma Ying , Fu Liwu , Chen Xiaoyuan 
Published: November 2017

AbstractThe delivery of therapeutic peptides for diabetes therapy is compromised by short half-lives of drugs with the consequent need for multiple daily injections that reduce patient compliance and increase treatment cost. In this study, we demonstrate a smart exendin-4 (Ex4) delivery device based on microneedle (MN)-array patches integrated with dual mineralized particles separately containing Ex4 and glucose oxidase (GOx). The dual mineralized particle-based system can specifically release Ex4 while immobilizing GOx as a result of the differential response to the microenvironment induced by biological stimuli. In this manner, the system enables glucose-responsive and closed-loop release to significantly improve Ex4 therapeutic performance. Moreover, integration of mineralized particles can enhance the mechanical strength of alginate-based MN by crosslinking to facilitate skin penetration, thus supporting painless and non-invasive transdermal administration. We believe this smart glucose-responsive Ex4 delivery holds great promise for type 2 diabetes therapy by providing safe, long-term, and on-demand Ex4 therapy.
Benchmarking organic mixed conductors for transistors
Authors: Inal Sahika , Malliaras George G. , Rivnay Jonathan 
Published: November 2017

AbstractOrganic mixed conductors have garnered significant attention in applications from bioelectronics to energy storage/generation. Their implementation in organic transistors has led to enhanced biosensing, neuromorphic function, and specialized circuits. While a narrow class of conducting polymers continues to excel in these new applications, materials design efforts have accelerated as researchers target new functionality, processability, and improved performance/stability. Materials for organic electrochemical transistors (OECTs) require both efficient electronic transport and facile ion injection in order to sustain high capacity. In this work, we show that the product of the electronic mobility and volumetric charge storage capacity (µC*) is the materials/system figure of merit; we use this framework to benchmark and compare the steady-state OECT performance of ten previously reported materials. This product can be independently verified and decoupled to guide materials design and processing. OECTs can therefore be used as a tool for understanding and designing new organic mixed conductors.
Feature-based learning improves adaptability without compromising precision
Authors: Farashahi Shiva , Rowe Katherine , Aslami Zohra , Lee Daeyeol , Soltani Alireza 
Published: November 2017

AbstractLearning from reward feedback is essential for survival but can become extremely challenging with myriad choice options. Here, we propose that learning reward values of individual features can provide a heuristic for estimating reward values of choice options in dynamic, multi-dimensional environments. We hypothesize that this feature-based learning occurs not just because it can reduce dimensionality, but more importantly because it can increase adaptability without compromising precision of learning. We experimentally test this hypothesis and find that in dynamic environments, human subjects adopt feature-based learning even when this approach does not reduce dimensionality. Even in static, low-dimensional environments, subjects initially adopt feature-based learning and gradually switch to learning reward values of individual options, depending on how accurately objects’ values can be predicted by combining feature values. Our computational models reproduce these results and highlight the importance of neurons coding feature values for parallel learning of values for features and objects.
Reconciling grain growth and shear-coupled grain boundary migration
Authors: Thomas Spencer L. , Chen Kongtao , Han Jian , Purohit Prashant K. , Srolovitz David J. 
Published: November 2017

AbstractConventional models for grain growth are based on the assumption that grain boundary (GB) velocity is proportional to GB mean curvature. We demonstrate via a series of molecular dynamics (MD) simulations that such a model is inadequate and that many physical phenomena occur during grain boundary migration for which this simple model is silent. We present a series of MD simulations designed to unravel GB migration phenomena and set it in a GB migration context that accounts for competing migration mechanisms, elasticity, temperature, and grain boundary crystallography. The resultant formulation is quantitative and validated through a series of atomistic simulations. The implications of this model for microstructural evolution is described. We show that consideration of GB migration mechanisms invites considerable complexity even under ideal conditions. However, that complexity also grants these systems enormous flexibility, and that flexibility is key to the decades-long success of conventional grain growth theories.
Single-cell absolute contact probability detection reveals chromosomes are organized by multiple low-frequency yet specific interactions
Authors: Cattoni Diego I. , Cardozo Gizzi Andrés M. , Georgieva Mariya , Di Stefano Marco , Valeri Alessandro , Chamousset Delphine , Houbron Christophe , Déjardin Stephanie , Fiche Jean-Bernard , González Inma , Chang Jia-Ming , Sexton Thomas , Marti-Renom Marc A. , Bantignies Frédéric , Cavalli Giacomo , Nollmann Marcelo 
Published: November 2017

AbstractAt the kilo- to megabase pair scales, eukaryotic genomes are partitioned into self-interacting modules or topologically associated domains (TADs) that associate to form nuclear compartments. Here, we combine high-content super-resolution microscopies with state-of-the-art DNA-labeling methods to reveal the variability in the multiscale organization of the Drosophila genome. We find that association frequencies within TADs and between TAD borders are below ~10%, independently of TAD size, epigenetic state, or cell type. Critically, despite this large heterogeneity, we are able to visualize nanometer-sized epigenetic domains at the single-cell level. In addition, absolute contact frequencies within and between TADs are to a large extent defined by genomic distance, higher-order chromosome architecture, and epigenetic identity. We propose that TADs and compartments are organized by multiple, small-frequency, yet specific interactions that are regulated by epigenetics and transcriptional state.
A galactic microquasar mimicking winged radio galaxies
Authors: Martí Josep , Luque-Escamilla Pedro L. , Bosch-Ramon Valentí , Paredes Josep M. 
Published: November 2017

AbstractA subclass of extragalactic radio sources known as winged radio galaxies has puzzled astronomers for many years. The wing features are detected at radio wavelengths as low-surface-brightness radio lobes that are clearly misaligned with respect to the main lobe axis. Different models compete to account for these peculiar structures. Here, we report observational evidence that the parsec-scale radio jets in the Galactic microquasar GRS 1758-258 give rise to a Z-shaped radio emission strongly reminiscent of the X and Z-shaped morphologies found in winged radio galaxies. This is the first time that such extended emission features are observed in a microquasar, providing a new analogy for its extragalactic relatives. From our observations, we can clearly favour the hydrodynamic backflow interpretation against other possible wing formation scenarios. Assuming that physical processes are similar, we can extrapolate this conclusion and suggest that this mechanism could also be at work in many extragalactic cases.
Simultaneous fabrication of line and dot dual nanopatterns using miktoarm block copolymer with photocleavable linker
Authors: Choi Chungryong , Park Jichoel , Vincent Joseph Kanniyambatti L. , Lee Jaeyong , Ahn Seonghyeon , Kwak Jongheon , Lee Kyu Seong , Kim Jin Kon 
Published: November 2017

AbstractBlock copolymers with various nanodomains, such as spheres, cylinders, and lamellae, have received attention for their applicability to nanolithography. However, those microdomains are determined by the volume fraction of one block. Meanwhile, nanopatterns with multiple shapes are required for the next-generation nanolithography. Although various methods have been reported to achieve dual nanopatterns, all the methods need sophisticated processes using E-beam. Here, we synthesized a miktoarm block copolymer capable of cleavage of one block by ultraviolet. Original cylindrical nanodomains of synthesized block copolymer were successfully transformed to lamellar nanodomains due to the change of molecular architecture by ultraviolet. We fabricated dual nanopatterns consisting of dots and lines at desired regions on a single substrate. We also prepared dual nanopatterns utilizing another phase transformation from spheres to cylinders in a block copolymer with higher interaction parameter. Since our concept has versatility to any block copolymer, it could be employed as next-generation nanolithography.
The rumen microbiome: an underexplored resource for novel antimicrobial discovery
Authors: Oyama Linda B. , Girdwood Susan E. , Cookson Alan R. , Fernandez-Fuentes Narcis , Privé Florence , Vallin Hannah E. , Wilkinson Toby J. , Golyshin Peter N. , Golyshina Olga V. , Mikut Ralf , Hilpert Kai , Richards Jennifer , Wootton Mandy , Edwards Joan E. , Maresca Marc , Perrier Josette , Lundy Fionnuala T. , Luo Yu , Zhou Mei , Hess Matthias , Mantovani Hilario C. , Creevey Christopher J. , Huws Sharon A. 
Published: November 2017

AbstractAntimicrobial peptides (AMPs) are promising drug candidates to target multi-drug resistant bacteria. The rumen microbiome presents an underexplored resource for the discovery of novel microbial enzymes and metabolites, including AMPs. Using functional screening and computational approaches, we identified 181 potentially novel AMPs from a rumen bacterial metagenome. Here, we show that three of the selected AMPs (Lynronne-1, Lynronne-2 and Lynronne-3) were effective against numerous bacterial pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). No decrease in MRSA susceptibility was observed after 25 days of sub-lethal exposure to these AMPs. The AMPs bound preferentially to bacterial membrane lipids and induced membrane permeability leading to cytoplasmic leakage. Topical administration of Lynronne-1 (10% w/v) to a mouse model of MRSA wound infection elicited a significant reduction in bacterial counts, which was comparable to treatment with 2% mupirocin ointment. Our findings indicate that the rumen microbiome may provide viable alternative antimicrobials for future therapeutic application.
Sorption Hysteresis of Light Hydrocarbons and Carbon Dioxide in Shale and Kerogen
Authors: Zhao Huangjing , Lai Zhiping , Firoozabadi Abbas 
Published: November 2017

AbstractWe present adsorption and desorption isotherms of methane, ethane, propane, n-butane and iso-butane as well as carbon dioxide for two shales and isolated kerogens determined by a gravimetric method. The sorption measurements of two shales were performed at three different temperatures, 308.15, 323.15, and 338.15 K. For the isolated kerogens, the measurements were conducted at 338.15 K. Methane and ethane sorption isotherms were measured to 35 bar. Carbon dioxide sorption isotherms were studied to 30 bar. Due to the low vapor pressure at room temperature, the sorption isotherms of propane, n-butane and iso-butane were measured to 8, 2, and 2 bar, respectively. The adsorptions of propane, n-butane, and iso-butane were much higher than methane at the highest pressures where the measurements were conducted. The adsorption of n-butane was 10 times higher than methane by mole at 2 bar, followed by iso-butane and propane. Our data show significant adsorption hysteresis in ethane, propane, n-butane and iso-butane. The most pronounced hysteresis was found in n-butane and iso-butane. Significant hysteresis is attributed to the reversible structural changes of kerogens. Dissolution of adsorbates into organic matter may also affect the hysteresis. This is the first report of propane and butane sorption isotherms in shales.
Acupuncture analgesia involves modulation of pain-induced gamma oscillations and cortical network connectivity
Authors: Hauck Michael , Schröder Sven , Meyer-Hamme Gesa , Lorenz Jürgen , Friedrichs Sunja , Nolte Guido , Gerloff Christian , Engel Andreas K. 
Published: November 2017

AbstractRecent studies support the view that cortical sensory, limbic and executive networks and the autonomic nervous system might interact in distinct manners under the influence of acupuncture to modulate pain. We performed a double-blind crossover design study to investigate subjective ratings, EEG and ECG following experimental laser pain under the influence of sham and verum acupuncture in 26 healthy volunteers. We analyzed neuronal oscillations and inter-regional coherence in the gamma band of 128-channel-EEG recordings as well as heart rate variability (HRV) on two experimental days. Pain ratings and pain-induced gamma oscillations together with vagally-mediated power in the high-frequency bandwidth (vmHF) of HRV decreased significantly stronger during verum than sham acupuncture. Gamma oscillations were localized in the prefrontal cortex (PFC), mid-cingulate cortex (MCC), primary somatosensory cortex and insula. Reductions of pain ratings and vmHF-power were significantly correlated with increase of connectivity between the insula and MCC. In contrast, connectivity between left and right PFC and between PFC and insula correlated positively with vmHF-power without a relationship to acupuncture analgesia. Overall, these findings highlight the influence of the insula in integrating activity in limbic-saliency networks with vagally mediated homeostatic control to mediate antinociception under the influence of acupuncture.
Similarities between acylcarnitine profiles in large for gestational age newborns and obesity
Authors: Sánchez-Pintos Paula , de Castro Maria-Jose , Roca Iria , Rite Segundo , López Miguel , Couce Maria-Luz 
Published: November 2017

AbstractLarge for gestational age (LGA) newborns have an increased risk of obesity, insulin resistance, and metabolic syndrome. Acylcarnitine profiles in obese children and adults are characterized by increased levels of C3, C5, and certain medium-chain (C12) and long-chain (C14:1 and C16) acylcarnitines. C2 is also increased in insulin-resistant states. In this 1-year observational study of 2514 newborns (246 LGA newborns, 250 small for gestational age (GA) newborns, and 2018 appropriate for GA newborns), we analyzed and compared postnatal acylcarnitine profiles in LGA newborns with profiles described for obese individuals. Acylcarnitine analysis was performed by tandem mass spectrometry on dried-blood spots collected on day 3 of life. LGA newborns had higher levels of total short-chain acylcarnitines (p < 0.001), C2 (p < 0.01) and C3 (p < 0.001) acylcarnitines, and all C12, C14, and C16 acylcarnitines except C12:1. They also had a higher tendency towards carnitine insufficiency (p < 0.05) and carnitine deficiency (p < 0.001). No significant differences were observed between LGA newborns born to mothers with or without a history of gestational diabetes. This novel study describes a postnatal acylcarnitine profile in LGA with higher levels of C2, C3, total acylcarnitines, and total short-chain acylcarnitines that is characteristic of childhood and adult obesity and linked to an unhealthy metabolic phenotype.
Computational derivation of a molecular framework for hair follicle biology from disease genes
Authors: Severin Rachel K. , Li Xinwei , Qian Kun , Mueller Andreas C. , Petukhova Lynn 
Published: November 2017

AbstractKnowledge about genetic drivers of disease increases the efficiency of interpreting patient DNA sequence and helps to identify and prioritize biological points of intervention. Discoveries of genes with single mutations exerting substantial phenotypic impact reliably provide new biological insight, although such approaches tend to generate knowledge that is disjointed from the complexity of biological systems governed by elaborate networks. Here we sought to facilitate diagnostic sequencing for hair disorders and assess the underlying biology by compiling an archive of 684 genes discovered in studies of monogenic disorders and identifying molecular annotations enriched by them. To demonstrate utility for this dataset, we performed two data driven analyses. First, we extracted and analyzed data implicating enriched signaling pathways and identified previously unrecognized contributions from Hippo signaling. Second, we performed hierarchical clustering on the entire dataset to investigate the underlying causal structure of hair disorders. We identified 35 gene clusters representing genetically derived biological modules that provide a foundation for the development of a new disease taxonomy grounded in biology, rather than clinical presentations alone. This Resource will be useful for diagnostic sequencing in patients with diseases affecting the hair follicle, improved characterization of hair follicle biology, and methods development in precision medicine.
Wind-generated Electricity in China: Decreasing Potential, Inter-annual Variability and Association with Changing Climate
Authors: Sherman Peter , Chen Xinyu , McElroy Michael B. 
Published: November 2017

AbstractChina hosts the world’s largest market for wind-generated electricity. The financial return and carbon reduction benefits from wind power are sensitive to changing wind resources. Wind data derived from an assimilated meteorological database are used here to estimate what the wind generated electricity in China would have been on an hourly basis over the period 1979 to 2015 at a geographical resolution of approximately 50 km × 50 km. The analysis indicates a secular decrease in generating potential over this interval, with the largest declines observed for western Inner Mongolia (15 ± 7%) and the northern part of Gansu (17 ± 8%), two leading wind investment areas. The decrease is associated with long-term warming in the vicinity of the Siberian High (SH), correlated also with the observed secular increase in global average surface temperatures. The long-term trend is modulated by variability relating to the Pacific Decadal Oscillation (PDO) and the Arctic Oscillation (AO). A linear regression model incorporating indices for the PDO and AO, as well as the declining trend, can account for the interannual variability of wind power, suggesting that advances in long-term forecasting could be exploited to markedly improve management of future energy systems.