bluuebunny/crossref_metadata_2025_split huggingface dataset:
Miocene Range Growth Along the Altyn Tagh Fault: Insights From Apatite Fission Track and (U‐Th)/He Thermochronometry in the Western Danghenan Shan, China
Authors: Yu Jingxing , Zheng Dewen , Pang Jianzhang , Wang Yizhou , Fox Matthew , Vermeesch Pieter , Li Chaopeng , Xiao Lin , Hao Yuqi , Wang Ying 
Published: August 2019

AbstractThe left‐lateral strike‐slip Altyn Tagh fault that defines the northern margin of the Tibetan Plateau plays a crucial role in accommodating the Cenozoic deformation related to the growth of plateau. However, the slip history along the fault remains highly debated. Here we report new 14–16 Ma apatite fission track (AFT) and 9–11 Ma apatite (U‐Th)/He (AHe) data in the western Danghenan Shan, north Tibet. Age‐elevation relationships and AFT/AHe age differences suggest a period of rapid exhumation with an average rate of 0.1–0.3 km/Ma from 16 to 9 Ma for this area. Thermal history modeling indicates that this was preceded by accelerated exhumation between the late Oligocene and middle Miocene (~15 Ma). A northward increase in AFT ages and asymmetric topography across the western Danghenan Shan indicate that the uplift and exhumation are mainly controlled by the thrust fault along the southern flank of the western Danghenan Shan. As the thrust fault is a branch of the Altyn Tagh fault, the rapid exhumation probably represents onset of the transition along the Altyn Tagh fault from left‐slip motion to crustal shortening in the Dangnenan Shan region. Our findings show that the middle Miocene deformation is not only recorded in the middle and northern Qilian Shan but also in the southwestern portion of the Qilian Shan, which favors a synchronous middle‐Miocene deformation model for the entire Qilian Shan.
Shale gas reserve evaluation by laboratory pyrolysis and gas holding capacity consistent with field data
Authors: Whitelaw Patrick , Uguna Clement N. , Stevens Lee A. , Meredith Will , Snape Colin E. , Vane Christopher H. , Moss-Hayes Vicky , Carr Andrew D. 
Published: August 2019

AbstractExploration for shale gas occurs in onshore basins, with two approaches used to predict the maximum gas in place (GIP) in the absence of production data. The first estimates adsorbed plus free gas held within pore space, and the second measures gas yields from laboratory pyrolysis experiments on core samples. Here we show the use of sequential high-pressure water pyrolysis (HPWP) to replicate petroleum generation and expulsion in uplifted onshore basins. Compared to anhydrous pyrolysis where oil expulsion is limited, gas yields are much lower, and the gas at high maturity is dry, consistent with actual shales. Gas yields from HPWP of UK Bowland Shales are comparable with those from degassed cores, with the ca. 1% porosity sufficient to accommodate the gas generated. Extrapolating our findings to the whole Bowland Shale, the maximum GIP equate to potentially economically recoverable reserves of less than 10 years of current UK gas consumption.
PAX8 activates metabolic genes via enhancer elements in Renal Cell Carcinoma
Authors: Bleu Melusine , Gaulis Swann , Lopes Rui , Sprouffske Kathleen , Apfel Verena , Holwerda Sjoerd , Pregnolato Marco , Yildiz Umut , Cordoʹ Valentina , Dost Antonella F. M. , Knehr Judith , Carbone Walter , Lohmann Felix , Lin Charles Y. , Bradner James E. , Kauffmann Audrey , Tordella Luca , Roma Guglielmo , Galli Giorgio G. 
Published: August 2019

AbstractTranscription factor networks shape the gene expression programs responsible for normal cell identity and pathogenic state. Using Core Regulatory Circuitry analysis (CRC), we identify PAX8 as a candidate oncogene in Renal Cell Carcinoma (RCC) cells. Validation of large-scale functional genomic screens confirms that PAX8 silencing leads to decreased proliferation of RCC cell lines. Epigenomic analyses of PAX8-dependent cistrome demonstrate that PAX8 largely occupies active enhancer elements controlling genes involved in various metabolic pathways. We selected the ferroxidase Ceruloplasmin (CP) as an exemplary gene to dissect PAX8 molecular functions. PAX8 recruits histone acetylation activity at bound enhancers looping onto the CP promoter. Importantly, CP expression correlates with sensitivity to PAX8 silencing and identifies a subset of RCC cases with poor survival. Our data identifies PAX8 as a candidate oncogene in RCC and provides a potential biomarker to monitor its activity.
Mesenchyme-free expansion and transplantation of adult alveolar progenitor cells: steps toward cell-based regenerative therapies
Authors: Weiner Aaron I. , Jackson Sergio R. , Zhao Gan , Quansah Kwaku K. , Farshchian Joseph N. , Neupauer Katherine M. , Littauer Elizabeth Q. , Paris Andrew J. , Liberti Derek C. , Scott Worthen G. , Morrisey Edward E. , Vaughan Andrew E. 
Published: August 2019

AbstractAlveolar type-2 (AT2) cells are necessary for the lung’s regenerative response to epithelial insults such as influenza. However, current methods to expand these cells rely on mesenchymal co-culture, complicating the possibility of transplantation following acute injury. Here we developed several mesenchyme-free culture conditions that promote growth of murine AT2 organoids. Transplanting dissociated AT2 organoids into influenza-infected mice demonstrated that organoids engraft and either proliferate as AT2 cells or unexpectedly adopt a basal cell-like fate associated with maladaptive regeneration. Alternatively, transplanted primary AT2 cells also robustly engraft, maintaining their AT2 lineage while replenishing the alveolar type-1 (AT1) cell population in the epithelium. Importantly, pulse oximetry revealed significant increase in blood-oxygen saturation in primary AT2 recipients, indicating that transplanted cells also confer increased pulmonary function after influenza. We further demonstrated that both acid installation and bleomycin injury models are also amenable to AT2 transplantation. These studies provide additional methods to study AT2 progenitor potential, while serving as proof-of-principle for adoptive transfer of alveolar progenitors in potential therapeutic applications.
Evolutionary characteristics of intergenic transcribed regions indicate rare novel genes and widespread noisy transcription in the Poaceae
Authors: Lloyd John P. , Bowman Megan J. , Azodi Christina B. , Sowers Rosalie P. , Moghe Gaurav D. , Childs Kevin L. , Shiu Shin-Han 
Published: August 2019

AbstractExtensive transcriptional activity occurring in intergenic regions of genomes has raised the question whether intergenic transcription represents the activity of novel genes or noisy expression. To address this, we evaluated cross-species and post-duplication sequence and expression conservation of intergenic transcribed regions (ITRs) in four Poaceae species. Among 43,301 ITRs across the four species, 34,460 (80%) are species-specific. ITRs found across species tend to be more divergent in expression and have more recent duplicates compared to annotated genes. To assess if ITRs are functional (under selection), machine learning models were established inOryza sativa(rice) that could accurately distinguish between phenotype genes and pseudogenes (area under curve-receiver operating characteristic = 0.94). Based on the models, 584 (8%) and 4391 (61%) rice ITRs are classified as likely functional and nonfunctional with high confidence, respectively. ITRs with conserved expression and ancient retained duplicates, features that were not part of the model, are frequently classified as likely-functional, suggesting these characteristics could serve as pragmatic rules of thumb for identifying candidate sequences likely to be under selection. This study also provides a framework to identify novel genes using comparative transcriptomic data to improve genome annotation that is fundamental for connecting genotype to phenotype in crop and model systems.
Early functional alterations in membrane properties and neuronal degeneration are hallmarks of progressive hearing loss in NOD mice
Authors: Lee Jeong Han , Park Seojin , Perez-Flores Maria C. , Wang Wenying , Kim Hyo Jeong , Izu Leighton , Gratton Michael Anne , Chiamvimonvat Nipavan , Yamoah Ebenezer N. 
Published: August 2019

AbstractPresbycusis or age-related hearing loss (ARHL) is the most common sensory deficit in the human population. A substantial component of the etiology stems from pathological changes in sensory and non-sensory cells in the cochlea. Using a non-obese diabetic (NOD) mouse model, we have characterized changes in both hair cells and spiral ganglion neurons that may be relevant for early signs of age-related hearing loss (ARHL). We demonstrate that hair cell loss is preceded by, or in parallel with altered primary auditory neuron functions, and latent neurite retraction at the hair cell-auditory neuron synapse. The results were observed first in afferent inner hair cell synapse of type I neurites, followed by type II neuronal cell-body degeneration. Reduced membrane excitability and loss of postsynaptic densities were some of the inaugural events before any outward manifestation of hair bundle disarray and hair cell loss. We have identified profound alterations in type I neuronal membrane properties, including a reduction in membrane input resistance, prolonged action potential latency, and a decrease in membrane excitability. The resting membrane potential of aging type I neurons in the NOD, ARHL model, was significantly hyperpolarized, and analyses of the underlying membrane conductance showed a significant increase in K+ currents. We propose that attempts to alleviate some forms of ARHL should include early targeted primary latent neural degeneration for effective positive outcomes.
Prediction of Treatment Response to Neoadjuvant Chemotherapy for Breast Cancer via Early Changes in Tumor Heterogeneity Captured by DCE-MRI Registration
Authors: Jahani Nariman , Cohen Eric , Hsieh Meng-Kang , Weinstein Susan P. , Pantalone Lauren , Hylton Nola , Newitt David , Davatzikos Christos , Kontos Despina 
Published: August 2019

AbstractWe analyzed DCE-MR images from 132 women with locally advanced breast cancer from the I-SPY1 trial to evaluate changes of intra-tumor heterogeneity for augmenting early prediction of pathologic complete response (pCR) and recurrence-free survival (RFS) after neoadjuvant chemotherapy (NAC). Utilizing image registration, voxel-wise changes including tumor deformations and changes in DCE-MRI kinetic features were computed to characterize heterogeneous changes within the tumor. Using five-fold cross-validation, logistic regression and Cox regression were performed to model pCR and RFS, respectively. The extracted imaging features were evaluated in augmenting established predictors, including functional tumor volume (FTV) and histopathologic and demographic factors, using the area under the curve (AUC) and the C-statistic as performance measures. The extracted voxel-wise features were also compared to analogous conventional aggregated features to evaluate the potential advantage of voxel-wise analysis. Voxel-wise features improved prediction of pCR (AUC = 0.78 (±0.03) vs 0.71 (±0.04), p < 0.05 and RFS (C-statistic = 0.76 ( ± 0.05), vs 0.63 ( ± 0.01)), p < 0.05, while models based on analogous aggregate imaging features did not show appreciable performance changes (p > 0.05). Furthermore, all selected voxel-wise features demonstrated significant association with outcome (p < 0.05). Thus, precise measures of voxel-wise changes in tumor heterogeneity extracted from registered DCE-MRI scans can improve early prediction of neoadjuvant treatment outcomes in locally advanced breast cancer.
Investigating appropriate molecular and chemical methods for ingredient identity testing of plant-based protein powder dietary supplements
Authors: Faller Adam C. , Arunachalam Thirugnanasambandam , Shanmughanandhan Dhivya , Kesanakurti Prasad , Shehata Hanan R. , Ragupathy Subramanyam , Newmaster Steven G. 
Published: August 2019

AbstractPlant-based protein powders are rapidly growing in popularity, and outdated quality assurance tools expose vulnerabilities to adulteration via different methods of “protein spiking”. Adequate diagnostic tools are urgently needed to be able to authenticate protein source ingredients and screen for potential adulterants. We explored the application of three diagnostic tools for ingredient identification: targeted PCR with Sanger sequencing, NGS, and LC-MS/MS. We collected 33 samples of common commercial products from the plant-based protein powder market and sought to identify botanical components using the three technologies. We found success in detection with all approaches, with at least one main protein source being identified by at least one approach in all samples. The investigation uncovered challenges to data collection or result interpretation with each technology including but not limited to amplification biases with PCR technologies, potential influence of DNA degradation, and issues with protein solubility during isolation. Ultimately, each platform demonstrated utility along with certain caveats, which epitomized the importance of orthogonality of testing.
Tree-ring correlations suggest links between moderate earthquakes and distant rockfalls in the Patagonian Cordillera
Authors: Stoffel M. , Ballesteros Cánovas J. A. , Luckman B. H. , Casteller A. , Villalba R. 
Published: August 2019

AbstractEarthquakes with magnitudes M > 7 can trigger large landslides and rockfalls at epicenter distances of up to 400 km, whereas moderate shaking (M = 5–7) is generally thought to result in abundant co-seismic mass movements in the vicinity of the epicenter. Although one might anticipate that large magnitude earthquakes off the Chilean coast would result in abundant rockfall in the Patagonian Cordillera, only limited research has explored this hypothesis. Here, we use tree-ring records from 63 cross-sections of century-old (103.9 ± 40.1 yr) Nothofagus pumilio trees to develop a calendar-dated record of small rockfall events (101–102 m3) on a talus slope located next to Monte Fitz Roy (El Chaltén, Argentina; 49°4′S, 72°57′W). The resulting rockfall record is used to infer that subduction zone seismicity at the Triple Junction and intraplate shaking around Lago Argentino almost systematically caused rockfall activity at this site, even if seismicity occurred at large distances (up to 300 km away) and with moderate intensity (M = 5–7). About one third of the rockfalls are triggered by factors other than earthquakes, predominantly in spring when freeze-thaw cycles occur frequently at the site. Despite the fact that seismicity is not the only trigger of rockfall activity at Cerro Crestón, at the foot of Monte Vespignani, we conclude that, in regions where topographic amplification plays a role, small rockfalls can be triggered by earthquakes of moderate intensity at large distances from the epicenter.
Long-tailed macaques extract statistical information from repeated types of events to make rational decisions under uncertainty
Authors: Placì Sarah , Padberg Marie , Rakoczy Hannes , Fischer Julia 
Published: August 2019

AbstractHuman children and apes seem to be intuitive statisticians when making predictions from populations of objects to randomly drawn samples, whereas monkeys seem not to be. Statistical reasoning can also be investigated in tasks in which the probabilities of different possibilities must be inferred from relative frequencies of events, but little is known about the performance of nonhuman primates in such tasks. In the current study, we investigated whether long-tailed macaques extract statistical information from repeated types of events to make predictions under uncertainty. In each experiment, monkeys first experienced the probability of rewards associated with different factors separately. In a subsequent test trial, monkeys could then choose between the different factors presented simultaneously. In Experiment 1, we tested whether long-tailed macaques relied on probabilities and not on a comparison of absolute quantities to make predictions. In Experiment 2 and 3 we varied the nature of the predictive factors and the complexity of the covariation structure between rewards and factors. Results indicate that long-tailed macaques extract statistical information from repeated types of events to make predictions and rational decisions under uncertainty, in more or less complex scenarios. These findings suggest that the presentation format affects the monkeys’ statistical reasoning abilities.
Observation of angle-dependent mode conversion and mode hopping in 2D annular antidot lattice
Authors: Porwal Nikita , De Anulekha , Mondal Sucheta , Dutta Koustuv , Choudhury Samiran , Sinha Jaivardhan , Barman Anjan , Datta P. K. 
Published: August 2019

AbstractWe report spin-wave excitations in annular antidot lattice fabricated from 15 nm-thin Ni80Fe20 film. The nanodots of 170 nm diameters are embedded in the 350 nm (diameter) antidot lattice to form the annular antidot lattice, which is arranged in a square lattice with edge-to-edge separation of 120 nm. A strong anisotropy in the spin-wave modes are observed with the change in orientation angle (ϕ) of the in-plane bias magnetic field by using Time-resolved Magneto-optic Kerr microscope. A flattened four-fold rotational symmetry, mode hopping and mode conversion leading to mode quenching for three prominent spin-wave modes are observed in this lattice with the variation of the bias field orientation. Micromagnetic simulations enable us to successfully reproduce the measured evolution of frequencies with the orientation of bias magnetic field, as well as to identify the spatial profiles of the modes. The magnetostatic field analysis, suggest the existence of magnetostatic coupling between the dot and antidot in annular antidot sample. Further local excitations of some selective spin-wave modes using numerical simulations showed the anisotropic spin-wave propagation through the lattice.
S1P2 contributes to microglial activation and M1 polarization following cerebral ischemia through ERK1/2 and JNK
Authors: Sapkota Arjun , Gaire Bhakta Prasad , Kang Min-Gu , Choi Ji Woong 
Published: August 2019

AbstractSphingosine 1-phosphate (S1P) signaling has emerged as a drug target in cerebral ischemia. Among S1P receptors, S1P2 was recently identified to mediate ischemic brain injury. But, pathogenic mechanisms are not fully identified, particularly in view of microglial activation, a core pathogenesis in cerebral ischemia. Here, we addressed whether microglial activation is the pathogenesis of S1P2-mediated brain injury in mice challenged with transient middle cerebral artery occlusion (tMCAO). To suppress S1P2 activity, its specific antagonist, JTE013 was given orally to mice immediately after reperfusion. JTE013 administration reduced the number of activated microglia and reversed their morphology from amoeboid to ramified microglia in post-ischemic brain after tMCAO challenge, along with attenuated microglial proliferation. Moreover, JTE013 administration attenuated M1 polarization in post-ischemic brain. This S1P2-directed M1 polarization appeared to occur in activated microglia, which was evidenced upon JTE013 exposure in vivo as suppressed M1-relevant NF-κB activation in activated microglia of post-ischemic brain. Moreover, JTE013 exposure or S1P2 knockdown reduced expression levels of M1 markers in vitro in lipopolysaccharide-driven M1 microglia. Additionally, suppressing S1P2 activity attenuated activation of M1-relevant ERK1/2 and JNK in post-ischemic brain or lipopolysaccharide-driven M1 microglia. Overall, our study demonstrated that S1P2 regulated microglial activation and M1 polarization in post-ischemic brain.
Upregulation of miR-17-92 cluster is associated with progression and lymph node metastasis in oesophageal adenocarcinoma
Authors: Plum Patrick Sven , Warnecke-Eberz Ute , Drebber Uta , Chon Seung-Hun , Alakus Hakan , Hölscher Arnulf Heinrich , Quaas Alexander , Bruns Christiane Josephine , Gockel Ines , Lorenz Dietmar , Metzger Ralf , Bollschweiler Elfriede 
Published: August 2019

AbstractThe occurrence of lymph node metastasis (LNM) and depth of tumour infiltration are significant prognostic factors in oesophageal adenocarcinoma (OAC), however no reliable prognostic biomarkers have been established so far. Aim of this study was to characterize microRNAs (miRs) of OAC patients, who primarily underwent oesophagectomy, in order to identify specific alterations during tumour progression and LNM. MicroRNA array-based quantification analysis of 754 miRs, including tumour specimens of 12 patients with pT2 OAC from three different centres (detection group), was performed. We identified miR-17, miR-19a/b, miR-20a, and miR-106a, showing the best predictive power for LNM. These miRs were validated by quantitative real time-PCR (qRT-PCR) in 43 patients with different tumour stages (pT1: n = 21; pT2: n = 12 and pT3: n = 10) (training group) (p < 0.05), demonstrating that increasing levels of identified miRs were associated with advanced depth of tumour infiltration. These findings were verified in another independent group of 46 pT2 OAC patients (validation group). Quantitative RT-PCR analysis of the miR-panel confirmed these results except for miR-19a (p < 0.05 each). Logistic regression analysis identified miR-17 and miR-20a (p = 0.025 and p = 0.022, respectively) to be independent variables for prediction of LNM. The mathematical prediction model was used in the validation group, and the estimated prognosis was compared to the actual postsurgical follow-up. This comprehensive data demonstrated the importance of miR-17-92 cluster and miR-106a for progression as well as LNM in OAC indicating that those might be feasible prognostic biomarkers.
Why digital medicine depends on interoperability
Authors: Lehne Moritz , Sass Julian , Essenwanger Andrea , Schepers Josef , Thun Sylvia 
Published: August 2019

AbstractDigital data are anticipated to transform medicine. However, most of today’s medical data lack interoperability: hidden in isolated databases, incompatible systems and proprietary software, the data are difficult to exchange, analyze, and interpret. This slows down medical progress, as technologies that rely on these data – artificial intelligence, big data or mobile applications – cannot be used to their full potential. In this article, we argue that interoperability is a prerequisite for the digital innovations envisioned for future medicine. We focus on four areas where interoperable data and IT systems are particularly important: (1) artificial intelligence and big data; (2) medical communication; (3) research; and (4) international cooperation. We discuss how interoperability can facilitate digital transformation in these areas to improve the health and well-being of patients worldwide.
Up-regulated ENO1 promotes the bladder cancer cell growth and proliferation via regulating β-catenin
Authors: Ji Mingfei , Wang Zhijun , Chen Jie , Gu Liqiong , Chen Ming , Ding Yelei , Liu Tao 
Published: August 2019

Abstract
Bladder cancer (BC) is the ninth most common malignancy throughout the world. The molecular mechanisms of this disease remain largely unclear. The glycolytic enzyme enolase 1 (ENO1) has been shown to regulate the development of various cancers. However, the significance of ENO1 in BC is underdetermined. In this study, we found that ENO1 was highly expressed in BC tissues and cells. High expression of ENO1 was associated with the poor survival of BC patients. Using lentivirus-mediated knockdown and over-expression, we revealed that ENO1 was critical for the growth and proliferation of BC cells. ENO1 over-expression also promoted the proliferation of SV-HUC-1 cells. At the molecular level, the cell cycle and apoptosis related genes were regulated by ENO1. β-catenin expression was positively regulated by ENO1. Furthermore, ectopic expression of β-catenin reversed the effect of ENO1 knockdown on T24 cell proliferation and growth. Opposite results were observed in β-catenin knockdown T24 cells. Our findings suggested that ENO1 functioned as an oncogene in BC through regulating cell cycle, apoptosis and β-catenin. Targeting ENO1/β-catenin cascade may benefit for BC patients.