bluuebunny/crossref_metadata_2025_split huggingface dataset:
ADAM12 is a circulating marker for stromal activation in pancreatic cancer and predicts response to chemotherapy
Authors: Veenstra V. L. , Damhofer H. , Waasdorp C. , van Rijssen L. B. , van de Vijver M. J. , Dijk F. , Wilmink H. W. , Besselink M. G. , Busch O. R. , Chang D. K. , Bailey P. J. , Biankin A. V. , Kocher H. M. , Medema J. P. , Li J. S. , Jiang R. , Pierce D. W. , van Laarhoven H. W. M. , Bijlsma M. F. 
Published: November 2018

AbstractPancreatic ductal adenocarcinoma (PDAC) is characterized by abundant stroma that harbors tumor-promoting properties. No good biomarkers exist to monitor the effect of stromal targeting therapies or to predict response. We set out to identify such non-invasive markers for PDAC stroma and predict response to therapy. Gene expression datasets, co-culture experiments, xenografts, and patient samples were analyzed. Serum samples were measured from a cohort of 58 resected patients, and 87 metastatic or locally advanced PDAC patients. Baseline and follow-up levels were assessed in 372 additional metastatic PDAC patients who received nab-paclitaxel with gemcitabine (n = 184) or gemcitabine monotherapy (n = 188) in the phase III MPACT trial. Increased levels of ADAM12 were found in PDAC patients compared to healthy controls (p < 0.0001, n = 157 and n = 38). High levels of ADAM12 significantly associated with poor outcome in resected PDAC (HR 2.07, p = 0.04). In the MPACT trial survival was significantly longer for patients who received nab-paclitaxel and had undetectable ADAM12 levels before treatment (OS 12.3 m vs 7.9 m p = 0.0046). Consistently undetectable or decreased ADAM12 levels during treatment significantly associated with longer survival as well (OS 14.4 m and 11.2 m, respectively vs 8.3, p = 0.0054). We conclude that ADAM12 is a blood-borne proxy for stromal activation, the levels of which have prognostic significance and correlate with treatment benefit.
Glucocorticoid-mediated ER-mitochondria contacts reduce AMPA receptor and mitochondria trafficking into cell terminus via microtubule destabilization
Authors: Choi Gee Euhn , Oh Ji Young , Lee Hyun Jik , Chae Chang Woo , Kim Jun Sung , Jung Young Hyun , Han Ho Jae 
Published: November 2018

AbstractGlucocorticoid, a major risk factor of Alzheimer’s disease (AD), is widely known to promote microtubule dysfunction recognized as the early pathological feature that culminates in memory deficits. However, the exact glucocorticoid receptor (GR)-mediated mechanism of how glucocorticoid triggers microtubule destabilization and following intracellular transport deficits remains elusive. Therefore, we investigated the effect of glucocorticoid on microtubule instability and cognitive impairment using male ICR mice and human neuroblastoma SH-SY5Y cells. The mice group that was exposed to corticosteroid, the major glucocorticoid form of rodents, showed reduced trafficking of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) 1/2 and mitochondria, which are necessary for memory establishment, into the synapse due to microtubule destabilization. In SH-SY5Y cells, cortisol, the major glucocorticoid form of humans, also decreased microtubule stability represented by reduced acetylated α-tubulin to tyrosinated α-tubulin ratio (A/T ratio), depending on the mitochondria GR-mediated pathway. Cortisol translocated the Hsp70-bound GR into mitochondria which thereafter promoted GR-Bcl-2 interaction. Increased ER-mitochondria connectivity via GR-Bcl-2 coupling led to mitochondrial Ca2+ influx, which triggered mTOR activation. Subsequent autophagy inhibition by mTOR phosphorylation increased SCG10 protein levels via reducing ubiquitination of SCG10, eventually inducing microtubule destabilization. Thus, failure of trafficking AMPAR1/2 and mitochondria into the cell terminus occurred by kinesin-1 detachment from microtubules, which is responsible for transporting organelles towards periphery. However, the mice exposed to pretreatment of microtubule stabilizer paclitaxel showed the restored translocation of AMPAR1/2 or mitochondria into synapses and improved memory function compared to corticosterone-treated mice. In conclusion, glucocorticoid enhances ER-mitochondria coupling which evokes elevated SCG10 and microtubule destabilization dependent on mitochondrial GR. This eventually leads to memory impairment through failure of AMPAR1/2 or mitochondria transport into cell periphery.
The structure and function of the global citrus rhizosphere microbiome
Authors: Xu Jin , Zhang Yunzeng , Zhang Pengfan , Trivedi Pankaj , Riera Nadia , Wang Yayu , Liu Xin , Fan Guangyi , Tang Jiliang , Coletta-Filho Helvécio D. , Cubero Jaime , Deng Xiaoling , Ancona Veronica , Lu Zhanjun , Zhong Balian , Roper M. Caroline , Capote Nieves , Catara Vittoria , Pietersen Gerhard , Vernière Christian , Al-Sadi Abdullah M. , Li Lei , Yang Fan , Xu Xun , Wang Jian , Yang Huanming , Jin Tao , Wang Nian 
Published: November 2018

AbstractCitrus is a globally important, perennial fruit crop whose rhizosphere microbiome is thought to play an important role in promoting citrus growth and health. Here, we report a comprehensive analysis of the structural and functional composition of the citrus rhizosphere microbiome. We use both amplicon and deep shotgun metagenomic sequencing of bulk soil and rhizosphere samples collected across distinct biogeographical regions from six continents. Predominant taxa include Proteobacteria, Actinobacteria, Acidobacteria and Bacteroidetes. The core citrus rhizosphere microbiome comprises Pseudomonas, Agrobacterium, Cupriavidus, Bradyrhizobium, Rhizobium, Mesorhizobium, Burkholderia, Cellvibrio, Sphingomonas, Variovorax and Paraburkholderia, some of which are potential plant beneficial microbes. We also identify over-represented microbial functional traits mediating plant-microbe and microbe-microbe interactions, nutrition acquisition and plant growth promotion in citrus rhizosphere. The results provide valuable information to guide microbial isolation and culturing and, potentially, to harness the power of the microbiome to improve plant production and health.
Hybrid perovskite light emitting diodes under intense electrical excitation
Authors: Kim Hoyeon , Zhao Lianfeng , Price Jared S. , Grede Alex J. , Roh Kwangdong , Brigeman Alyssa N. , Lopez Mike , Rand Barry P. , Giebink Noel C. 
Published: November 2018

AbstractHybrid perovskite semiconductors represent a promising platform for color-tunable light emitting diodes (LEDs) and lasers; however, the behavior of these materials under the intense electrical excitation required for electrically-pumped lasing remains unexplored. Here, we investigate methylammonium lead iodide-based perovskite LEDs under short pulsed drive at current densities up to 620 A cm−2. At low current density (J < 10 A cm−2), we find that the external quantum efficiency (EQE) depends strongly on the time-averaged history of the pulse train and show that this curiosity is associated with slow ion movement that changes the internal field distribution and trap density in the device. The impact of ions is less pronounced in the high current density regime (J > 10 A cm−2), where EQE roll-off is dominated by a combination of Joule heating and charge imbalance yet shows no evidence of Auger loss, suggesting that operation at kA cm−2 current densities relevant for a laser diode should be within reach.
Improved reference genome of Aedes aegypti informs arbovirus vector control
Authors: Matthews Benjamin J. , Dudchenko Olga , Kingan Sarah B. , Koren Sergey , Antoshechkin Igor , Crawford Jacob E. , Glassford William J. , Herre Margaret , Redmond Seth N. , Rose Noah H. , Weedall Gareth D. , Wu Yang , Batra Sanjit S. , Brito-Sierra Carlos A. , Buckingham Steven D. , Campbell Corey L. , Chan Saki , Cox Eric , Evans Benjamin R. , Fansiri Thanyalak , Filipović Igor , Fontaine Albin , Gloria-Soria Andrea , Hall Richard , Joardar Vinita S. , Jones Andrew K. , Kay Raissa G. G. , Kodali Vamsi K. , Lee Joyce , Lycett Gareth J. , Mitchell Sara N. , Muehling Jill , Murphy Michael R. , Omer Arina D. , Partridge Frederick A. , Peluso Paul , Aiden Aviva Presser , Ramasamy Vidya , Rašić Gordana , Roy Sourav , Saavedra-Rodriguez Karla , Sharan Shruti , Sharma Atashi , Smith Melissa Laird , Turner Joe , Weakley Allison M. , Zhao Zhilei , Akbari Omar S. , Black William C. , Cao Han , Darby Alistair C. , Hill Catherine A. , Johnston J. Spencer , Murphy Terence D. , Raikhel Alexander S. , Sattelle David B. , Sharakhov Igor V. , White Bradley J. , Zhao Li , Aiden Erez Lieberman , Mann Richard S. , Lambrechts Louis , Powell Jeffrey R. , Sharakhova Maria V. , Tu Zhijian , Robertson Hugh M. , McBride Carolyn S. , Hastie Alex R. , Korlach Jonas , Neafsey Daniel E. , Phillippy Adam M. , Vosshall Leslie B. 
Published: November 2018

AbstractFemale Aedes aegypti mosquitoes infect more than 400 million people each year with dangerous viral pathogens including dengue, yellow fever, Zika and chikungunya. Progress in understanding the biology of mosquitoes and developing the tools to fight them has been slowed by the lack of a high-quality genome assembly. Here we combine diverse technologies to produce the markedly improved, fully re-annotated AaegL5 genome assembly, and demonstrate how it accelerates mosquito science. We anchored physical and cytogenetic maps, doubled the number of known chemosensory ionotropic receptors that guide mosquitoes to human hosts and egg-laying sites, provided further insight into the size and composition of the sex-determining M locus, and revealed copy-number variation among glutathione S-transferase genes that are important for insecticide resistance. Using high-resolution quantitative trait locus and population genomic analyses, we mapped new candidates for dengue vector competence and insecticide resistance. AaegL5 will catalyse new biological insights and intervention strategies to fight this deadly disease vector.
The hippocampus underlies the association between self-esteem and physical health
Authors: Lu Huanhua , Li Xueting , Wang Yinan , Song Yiying , Liu Jia 
Published: November 2018

AbstractSelf-esteem refers to the extent to which we feel positive or negative about ourselves, and reflects an individual’s subjective evaluation of personal worth and attitudes about the self. As one kind of positive psychosocial resources, high self-esteem has been found to buffer the effects of stress on physical health. However, little is known about the possible neural basis underlying the association between physical health and self-esteem. In the present study, we investigated whether the hippocampus served as a neuroanatomical basis for the association between self-esteem and physical health in a large population of healthy young adults. We examined self-esteem and self-reported physical health with the Rosenberg Self Esteem Scale (RSES) and the Chinese Constitution Questionnaire (CCQ) respectively, and gray matter volume of the hippocampus was measured using magnetic resonance imaging. As expected, we found that individuals with higher levels of self-esteem had better self-reported physical health. Importantly, the mediation analysis showed that the gray matter volume of the hippocampus mediated the link between self-esteem and physical health, suggesting its critical role in the neural circuitry through which self-esteem is related to physical health.
p66Shc activation promotes increased oxidative phosphorylation and renders CNS cells more vulnerable to amyloid beta toxicity
Authors: Lone Asad , Harris Richard A. , Singh Olivia , Betts Dean H. , Cumming Robert C. 
Published: November 2018

AbstractA key pathological feature of Alzheimer’s disease (AD) is the accumulation of the neurotoxic amyloid beta (Aβ) peptide within the brains of affected individuals. Previous studies have shown that neuronal cells selected for resistance to Aβ toxicity display a metabolic shift from mitochondrial-dependent oxidative phosphorylation (OXPHOS) to aerobic glycolysis to meet their energy needs. The Src homology/collagen (Shc) adaptor protein p66Shc is a key regulator of mitochondrial function, ROS production and aging. Moreover, increased expression and activation of p66Shc promotes a shift in the cellular metabolic state from aerobic glycolysis to OXPHOS in cancer cells. Here we evaluated the hypothesis that activation of p66Shc in CNS cells promotes both increased OXPHOS and enhanced sensitivity to Aβ toxicity. The effect of altered p66Shc expression on metabolic activity was assessed in rodent HT22 and B12 cell lines of neuronal and glial origin respectively. Overexpression of p66Shc repressed glycolytic enzyme expression and increased both mitochondrial electron transport chain activity and ROS levels in HT22 cells. The opposite effect was observed when endogenous p66Shc expression was knocked down in B12 cells. Moreover, p66Shc activation in both cell lines increased their sensitivity to Aβ toxicity. Our findings indicate that expression and activation of p66Shc renders CNS cells more sensitive to Aβ toxicity by promoting mitochondrial OXPHOS and ROS production while repressing aerobic glycolysis. Thus, p66Shc may represent a potential therapeutically relevant target for the treatment of AD.
Real-time tropospheric delay retrieval with GPS, GLONASS, Galileo and BDS data
Authors: Pan Lin , Guo Fei 
Published: November 2018

AbstractThe precise point positioning (PPP) is a promising technology for the real-time retrieval of atmospheric parameters with a single receiver in anywhere, all-weather and any time. The real-time atmospheric parameters can be applied to the time-critical meteorology, such as the severe weather nowcasting. The PPP is a satellite-based technology. Multi-constellation integration can enhance satellite geometry and increase measurement redundancy so that the solutions of atmospheric parameters are expected to be improved. Currently, the Global Navigation Satellite System (GNSS) family includes recovered GLONASS and modernized GPS as well as the emerging Galileo and BDS. A week of GNSS observations from 160 stations are processed to retrieve the tropospheric zenith total delay (ZTD) in real time. The four-constellation mixed real-time precise products including satellite orbit and clock corrections are adopted, and their quality is evaluated. The performance of ZTD estimates is assessed in terms of accuracy and convergence time by comparing with final tropospheric ZTD products provided by two analysis centers. The ZTDs retrieved from different constellation combinations (i.e., GPS/GLONASS/Galileo/BDS, GPS/GLONASS, and GPS-only), different processing models for ionospheric delays (i.e., ionospheric-free (IF) combined PPP, and uncombined (UC) PPP), and different modes (i.e., real-time mode, and post-processing mode) are compared.
IL-23R Signaling Plays No Role in Myocardial Infarction
Authors: Engelowski Erika , Modares Nastaran Fazel , Gorressen Simone , Bouvain Pascal , Semmler Dominik , Alter Christina , Ding Zhaoping , Flögel Ulrich , Schrader Jürgen , Xu Haifeng , Lang Philipp A. , Fischer Jens , Floss Doreen M. , Scheller Jürgen 
Published: November 2018

AbstractIschemic heart diseases are the most frequent diseases in the western world. Apart from Interleukin (IL-)1, inflammatory therapeutic targets in the clinic are still missing. Interestingly, opposing roles of the pro-inflammatory cytokine IL-23 have been described in cardiac ischemia in mice. IL-23 is a composite cytokine consisting of p19 and p40 which binds to IL-23R and IL-12Rβ1 to initiate signal transduction characterized by activation of the Jak/STAT, PI3K and Ras/Raf/MAPK pathways. Here, we generate IL-23R-Y416FΔICD signaling deficient mice and challenged these mice in close- and open-chest left anterior descending coronary arteria ischemia/reperfusion experiments. Our experiments showed only minimal changes in all assayed parameters in IL-23R signaling deficient mice compared to wild-type mice in ischemia and for up to four weeks of reperfusion, including ejection fraction, endsystolic volume, enddiastolic volume, infarct size, gene regulation and α smooth muscle actin (αSMA) and Hyaluronic acid (HA) protein expression. Moreover, injection of IL-23 in wild-type mice after LAD ischemia/reperfusion had also no influence on the outcome of the healing phase. Our data showed that IL-23R deficiency has no effects in myocardial I/R.
Gene Expression Signatures Point to a Male Sex-Specific Lung Mesenchymal Cell PDGF Receptor Signaling Defect in Infants Developing Bronchopulmonary Dysplasia
Authors: Fulton Christina T. , Cui Tracy X. , Goldsmith Adam M. , Bermick Jennifer , Popova Antonia P. 
Published: November 2018

AbstractMale sex is a risk factor for development of bronchopulmonary dysplasia (BPD), a common chronic lung disease following preterm birth. We previously found that tracheal aspirate mesenchymal stromal cells (MSCs) from premature infants developing BPD show reduced expression of PDGFRα, which is required for normal lung development. We hypothesized that MSCs from male infants developing BPD exhibit a pathologic gene expression profile deficient in PDGFR and its downstream effectors, thereby favoring delayed lung development. In a discovery cohort of 6 male and 7 female premature infants, we analyzed the tracheal aspirate MSCs transcriptome. A unique gene signature distinguished MSCs from male infants developing BPD from all other MSCs. Genes involved in lung development, PDGF signaling and extracellular matrix remodeling were differentially expressed. We sought to confirm these findings in a second cohort of 13 male and 12 female premature infants. mRNA expression of PDGFRA, FGF7, WNT2, SPRY1, MMP3 and FOXF2 were significantly lower in MSCs from male infants developing BPD. In female infants developing BPD, tracheal aspirate levels of proinflammatory CCL2 and profibrotic Galectin-1 were higher compared to male infants developing BPD and female not developing BPD. Our findings support a notion for sex-specific differences in the mechanisms of BPD development.
The relative effects of forest amount, forest configuration, and urban matrix quality on forest breeding birds
Authors: Shoffner Alexandra , Wilson Andrew M. , Tang Wenwu , Gagné Sara A. 
Published: November 2018

AbstractUrbanization modifies landscape structure in three major ways that impact avian diversity in remnant habitat: habitat amount is reduced and habitat configuration and matrix quality are altered. The relative effects of these three components of landscape structure are relatively well-studied in agricultural landscapes, but little is known about the relative effect of urban matrix quality. We addressed this gap by investigating the relative effects of forest amount, forest configuration, and matrix quality, indicated by degree of urbanization and agriculture amount, on the diversity of three guilds of forest birds using data from 13,763 point counts from Pennsylvania, USA. Forest amount had the largest independent effect on forest bird diversity, followed by matrix quality, then forest configuration. In particular, urbanization had strong negative effects on the relative abundance and species evenness of all forest birds and the relative abundance of forest generalist birds. To our knowledge, these are the first results of the effect of urban matrix quality on forest bird relative abundance and species evenness independent of forest amount and forest configuration. Our results imply that conservation practitioners in human-modified landscapes prioritize maximizing forest amount, then reducing the effects of disturbances originating in the matrix, and then preserving large, spatially-dispersed forest patches to most effectively conserve forest birds.
Collagen density modulates triple-negative breast cancer cell metabolism through adhesion-mediated contractility
Authors: Mah Emma J. , Lefebvre Austin E. Y. T. , McGahey Gabrielle E. , Yee Albert F. , Digman Michelle A. 
Published: November 2018

AbstractExtracellular matrix (ECM) mechanical properties upregulate cancer invasion, cell contractility, and focal adhesion formation. Alteration in energy metabolism is a known characteristic of cancer cells (i.e., Warburg effect) and modulates cell invasion. There is little evidence to show if collagen density can alter cancer cell metabolism. We investigated changes in energy metabolism due to collagen density in five breast cell lines by measuring the fluorescence lifetime of NADH. We found that only triple-negative breast cancer cells, MDA-MB231 and MDA-MB468 cells, had an increased population of bound NADH, indicating an oxidative phosphorylation (OXPHOS) signature, as collagen density decreased. When inhibiting ROCK and cell contractility, MDA-MB231 cells on glass shifted from glycolysis (GLY) to OXPHOS, confirming the intricate relationship between mechanosensing and metabolism. MCF10A cells showed less significant changes in metabolism, shifting towards GLY as collagen density decreased. The MCF-7 and T-47D, less invasive breast cancer cells, compared to the MDA-MB231 and MDA-MB468 cells, showed no changes regardless of substrate. In addition, OXPHOS or GLY inhibitors in MDA-MB231 cells showed dramatic shifts from OXPHOS to GLY or vice versa. These results provide an important link between cellular metabolism, contractility, and collagen density in human breast cancer.
A single-cycle replicable Rift Valley fever phlebovirus vaccine carrying a mutated NSs confers full protection from lethal challenge in mice
Authors: Terasaki Kaori , Juelich Terry L. , Smith Jennifer K. , Kalveram Birte , Perez David D. , Freiberg Alexander N. , Makino Shinji 
Published: November 2018

AbstractRift Valley fever phlebovirus (RVFV) is a pathogen of Rift Valley fever, which is a mosquito-borne zoonotic disease for domestic livestock and humans in African countries. Currently, no approved vaccine is available for use in non-endemic areas. The MP-12 strain is so far the best live attenuated RVFV vaccine candidate because of its good protective efficacy in animal models. However, there are safety concerns for use of MP-12 in humans. We previously developed a single-cycle replicable MP-12 (scMP-12) which lacks NSs gene and undergoes only a single round of viral replication because of its impaired ability to induce membrane-membrane fusion. In the present study, we generated an scMP-12 mutant (scMP-12-mutNSs) carrying a mutant NSs, which degrades double-stranded RNA-dependent protein kinase R but does not inhibit host transcription. Immunization of mice with a single dose (105 PFU) of scMP-12-mutNSs elicited RVFV neutralizing antibodies and high titers of anti-N IgG production and fully protected the mice from lethal wild-type RVFV challenge. Immunogenicity and protective efficacy of scMP-12-mutNSs were better than scMP-12, demonstrating that scMP-12-mutNSs is a more efficacious vaccine candidate than scMP-12. Furthermore, our data suggested that RVFV vaccine efficacy can be improved by using this specific NSs mutant.