bluuebunny/crossref_metadata_2025_split huggingface dataset:
Autotaxin Regulates Maintenance of Ovarian Cancer Stem Cells through Lysophosphatidic Acid-Mediated Autocrine Mechanism
Authors: Seo Eun Jin , Kwon Yang Woo , Jang Il Ho , Kim Dae Kyoung , Lee Soo In , Choi Eun Jung , Kim Ki-Hyung , Suh Dong-Soo , Lee Jeong Hee , Choi Kyung Un , Lee Jae Won , Mok Hyuck Jun , Kim Kwang Pyo , Matsumoto Hirotaka , Aoki Junken , Kim Jae Ho 
Published: January 2016

Abstract
Ovarian cancer shows high mortality due to development of resistance to chemotherapy and relapse. Cancer stem cells (CSCs) have been suggested to be a major contributor in developing drug resistance and relapse in ovarian cancer. In this study, we isolated CSCs through sphere culture of A2780, SKOV3, OVCAR3 epithelial ovarian cancer cells and primary ovarian cancer cells from patients. We identified heat-stable factors secreted from ovarian CSCs stimulated migration and proliferation of CSCs. Mass spectrometry and ELISA analysis revealed that lysophosphatidic acid (LPA) was significantly elevated in CSC culture media compared with non-CSC culture media. Treatment of CSCs with LPA resulted in augmented CSC characteristics such as sphere-forming ability, resistance to anticancer drugs, tumorigenic potential in xenograft transplantation, and high expression of CSC-associated genes, including OCT4, SOX2, and aldehyde dehydrogenase 1. Treatment of CSCs with LPA receptor 1-specific inhibitors or silencing of LPA receptor 1 expression abrogated the LPA-stimulated CSC properties. Autotaxin, an LPA-producing enzyme, is highly secreted from ovarian CSCs, and pharmacological inhibition or knockdown of autotaxin markedly attenuated the LPA-producing, tumorigenic, and drug resistance potentials of CSCs. Clinicopathological analysis showed a significant survival disadvantage of patients with positive staining of autotaxin. In addition, we further identified that AKT1 activity was upregulated in ovarian CSCs through an LPA-dependent mechanism and silencing of AKT1 expression led to suppression of CSC characteristics. These results suggest that autotaxin-LPA-LPA receptor 1-AKT1 signaling axis is critical for maintaining CSC characteristics through an autocrine loop and provide a novel therapeutic target for ovarian CSCs.
Tryptophan biosynthesis is important for resistance to replicative stress in Saccharomyces cerevisiae
Authors: Godin Stephen K. , Lee Alison G. , Baird Jared M. , Herken Benjamin W. , Bernstein Kara A. 
Published: January 2016

AbstractAcute tryptophan depletion is used to induce low levels of serotonin in the brain. This method has been widely used in psychiatric studies to evaluate the effect of low levels of serotonin, and is generally considered a safe and reversible procedure. Here we use the budding yeast Saccharomyces cerevisiae to study the effects of tryptophan depletion on growth rate upon exposure to DNA‐damaging agents. Surprisingly, we found that budding yeast undergoing tryptophan depletion were more sensitive to DNA‐damaging agents such as methyl methanesulphonate (MMS) and hydroxyurea (HU). We found that this defect was independent of several DNA repair pathways, such as homologous recombination, base excision repair and translesion synthesis, and that this damage sensitivity was not due to impaired S‐phase signalling. Upon further analysis, we found that the DNA‐damage sensitivity of tryptophan depletion was likely due to impaired protein synthesis. These studies describe an important source of variance in budding yeast when using tryptophan as an auxotrophic marker, particularly on studies focusing on DNA repair, and suggest that further testing of the effect of tryptophan depletion on DNA repair in mammalian cells is warranted. Copyright © 2016 John Wiley & Sons, Ltd.
Laparoscopic Hiatal Hernia Repair in the Elderly Patient
Authors: Oor J. E. , Koetje J. H. , Roks D. J. , Nieuwenhuijs V. B. , Hazebroek E. J. 
Published: January 2016

AbstractBackgroundHiatal hernias (HH) are more common among elderly patients, with an increase in incidence with advancing age. Elderly patients frequently suffer from comorbidity, causing them to have an increased risk of perioperative mortality and morbidity. The aim of this study is to assess the safety of this procedure within elderly patients.MethodsWe performed a retrospective analysis of all patients with HH operated between July 2009 and May 2015 at two hospitals in the Netherlands specialized in antireflux surgery and HH repair. Mortality rates and short‐ and long‐term morbidity rates were compared between patients aged under 70 years and aged over 70 years.ResultsA total of 204 consecutive patients underwent laparoscopic HH repair at our institutions, of whom 121 were aged under 70 years and 83 were aged over 70 years. There was no mortality intraoperatively, nor during 30‐days follow‐up. Intraoperative complications occurred in 7 patients aged 70 years and over, with no significant differences compared to the patients aged under 70. The 30‐day morbidity rate did not significantly differ between the age groups, with an overall postoperative complication rate of 9.3 %. Only length of stay (LOS) was significantly longer in the elderly patients. Performing univariate analysis, only the occurrence of intraoperative complications was associated with 30‐day morbidity.ConclusionIn the present study, age was not associated with increased 30‐day morbidity or mortality following HH repair. Therefore, in carefully selected patients, age should not be used as an argument to withhold laparoscopic HH repair.
Production of biorenewable styrene: utilization of biomass-derived sugars and insights into toxicity
Authors: Lian Jieni , McKenna Rebekah , Rover Marjorie R , Nielsen David R , Wen Zhiyou , Jarboe Laura R 
Published: January 2016

Abstract
Fermentative production of styrene from glucose has been previously demonstrated in Escherichia coli. Here, we demonstrate the production of styrene from the sugars derived from lignocellulosic biomass depolymerized by fast pyrolysis. A previously engineered styrene-producing strain was further engineered for utilization of the anhydrosugar levoglucosan via expression of levoglucosan kinase. The resulting strain produced 240 ± 3 mg L−1 styrene from pure levoglucosan, similar to the 251 ± 3 mg L−1 produced from glucose. When provided at a concentration of 5 g L−1, pyrolytic sugars supported styrene production at titers similar to those from pure sugars, demonstrating the feasibility of producing this important industrial chemical from biomass-derived sugars. However, the toxicity of contaminant compounds in the biomass-derived sugars and styrene itself limit further gains in production. Styrene toxicity is generally believed to be due to membrane damage. Contrary to this prevailing wisdom, our quantitative assessment during challenge with up to 200 mg L−1 of exogenously provided styrene showed little change in membrane integrity; membrane disruption was observed only during styrene production. Membrane fluidity was also quantified during styrene production, but no changes were observed relative to the non-producing control strain. This observation that styrene production is much more damaging to the membrane integrity than challenge with exogenously supplied styrene provides insight into the mechanism of styrene toxicity and emphasizes the importance of verifying proposed toxicity mechanisms during production instead of relying upon results obtained during exogenous challenge.
Durable Late Blight Resistance in Potato Through Dynamic Varieties Obtained by Cisgenesis: Scientific and Societal Advances in the DuRPh Project
Authors: Haverkort A. J. , Boonekamp P. M. , Hutten R. , Jacobsen E. , Lotz L. A. P. , Kessel G. J. T. , Vossen J. H. , Visser R. G. F. 
Published: January 2016

Abstract
From 2006 through 2015, a research project on Durable Resistance in potato against Phytophthora (DuRPh) was carried out at Wageningen University and Research Centre. Its objective was to develop a proof of principle for durable resistance against late blight by cisgenesis. This public-funded project aimed at stimulating research on genetic modification and public debate on innovative genetic techniques. It was decided to clone and transfer late blight resistance (R) genes of crossable wild potato species (cisgenes) by Agrobacterium tumefaciens-mediated transformation without non-potato genes. A stack of multiple R genes were planned to be inserted into established varieties, thereby creating a dynamic variety in which the composition of the stacks may vary over space and time. Cisgenic plants were selected based on the expression of all inserted R genes and trueness-to-type. Within the project, 13 R genes from wild potato species were genetically mapped and three of them were cloned. Four varieties were transformed with one to three R genes. This was initially done using kanamycin resistance provided by a selectable marker gene of synthetic origin in order to quickly test the performance and stability of the introduced R genes and stacked R gene combinations. Once the functioning thereof was confirmed, marker-free transformations were conducted; thus, true cisgenic events were selected. The results about the different R genes, their chromosomal location, their specificity, the background dependence, the maximum size of a stack, its regeneration time and associated somaclonal variation frequency and its stability were studied. After selection and characterisation in the laboratory, the best cisgenic events were assessed in field trials for late blight resistance. This showed that inserted R genes were capable of turning a susceptible variety into a resistant one. Maximising longevity of the resistance was assured through resistance management research. It was shown that stacking of multiple R genes and monitoring how to deploy these stacks spatially and temporally could reduce fungicide use by over 80%. Communications through media and field demonstrations were manifold to allow public and policymakers to decide if cisgenesis is an acceptable tool to make potato farming more sustainable. Future deployment of the DuRPh strategy will depend largely on its status as a genetically modified crop or its exemption thereof. Worldwide near eradication of late blight would increase global annual potato production by close to 80 million tons, thereby contributing considerably to the needed additional global future food supply.
Absolute Stereochemistry of 1,2‐Diols from Lipids of Thermomicrobia
Authors: Lagutin Kirill , Wong Herbert , Vyssotski Mikhail , MacKenzie Andrew 
Published: January 2016

Abstract1,2‐Diol based phospholipids are a well‐known feature of bacteria from the class Thermomicrobia. Since these bacteria contain only lipids with an alkyldiol‐1‐phosphate backbone instead of sn‐glycero‐3‐phosphate, it is important to elucidate the stereochemistry of the 1,2‐diols. We have studied the absolute stereochemistry of long‐chain 1,2‐diols isolated from Thermorudis pharmacophila (formerly known as Thermomicrobia sp. WKT50.2) by nuclear magnetic resonance (NMR) using α‐methoxyphenylacetic acid (MPA). Low‐temperature (−60 °C) NMR of bis‐(R)‐MPA ester showed (R) stereochemistry of the 1,2‐diols. This is the first report concerning the stereochemistry of natural 1,2‐diols, which replace the glyceride moiety in phospholipids. The (R) stereochemistry of the diols is expected as it is the same configuration as for the common bacterial lipid backbone—sn‐glycero‐3‐phosphate. This is the first application of low‐temperature NMR of a single MPA derivative for assignment of stereochemistry of natural 1,2‐diols. The results were confirmed by the comparison of NMR data with bis‐(R)‐MPA ester of (R) and rac‐1,2‐octanediol.
Three‐arm age‐matched retrospective cohort study of obstetric outcomes of donor oocyte pregnancies
Authors: Jeve Yadava B. , Potdar Neelam , Opoku Albert , Khare Manjiri 
Published: January 2016

AbstractObjectiveTo evaluate and compare obstetric complications between women who conceived after oocyte donation and age‐matched control women who conceived spontaneously or by autologous in vitro fertilization (IVF).MethodsIn a retrospective cohort study, data were assessed from all women who conceived after oocyte donation and delivered a live neonate after 24 weeks of pregnancy between January 2007 and December 2014 at a UK hospital. Two age‐matched control groups—one containing women who conceived after autologous IVF and the other containing women who conceived spontaneously—were used for comparison. The primary study outcome was hypertensive disorders of pregnancy (pregnancy‐induced hypertension and pre‐eclampsia). Multivariate analysis was performed by logistic regression.ResultsEach group included 45 women. Hypertensive disorders in pregnancy affected 15 (33%) women in the study group, 3 (7%) women who conceived after autologous IVF, and 3 (7%) who conceived spontaneously. The risk of hypertensive disorders in pregnancy was significantly higher in the donor oocyte group (odds ratio 5.85, 95% confidence interval 1.42–23.9; P = 0.01).ConclusionWomen who conceived after oocyte donation had an increased risk of hypertensive disorders. Oocyte donation should be managed as an independent risk factor, and couples should be counselled appropriately.
Molecular pathogenesis of long QT syndrome type 2
Authors: Smith Jennifer L. , Anderson Corey L. , Burgess Don E. , Elayi Claude S. , January Craig T. , Delisle Brian P. 
Published: January 2016

AbstractThe molecular mechanisms underlying congenital long QT syndrome (LQTS) are now beginning to be understood. New insights into the etiology and therapeutic strategies are emerging from heterologous expression studies of LQTS‐linked mutant proteins, as well as inducible pluripotent stem cell derived cardiomyocytes (iPSC‐CMs) from LQTS patients. This review focuses on the major molecular mechanism that underlies LQTS type 2 (LQT2). LQT2 is caused by loss of function (LOF) mutations in KCNH2 (also known as the human Ether‐à‐go‐go‐Related Gene or hERG). Most LQT2‐linked mutations are missense mutations and functional studies suggest that ~90% of them disrupt the intracellular transport (trafficking) of KCNH2‐encoded Kv11.1 proteins to the cell membrane. Trafficking deficient LQT2 mutations disrupt Kv11.1 protein folding and misfolded Kv11.1 proteins are retained in the endoplasmic reticulum (ER) until they are degraded in the ER associated degradation pathway (ERAD). This review focuses on the quality control mechanisms in the ER that contribute to the folding and ERAD of Kv11.1 proteins; the mechanism for ER export of Kv11.1 proteins in the secretory pathway; different subclasses of trafficking deficient LQT2 mutations; and strategies being developed to mitigate or correct trafficking deficient LQT2‐related phenotypes.
Putting hell first: cruelty, historicism, and the missing moral theory of damnation
Authors: Perry John 
Published: January 2016

AbstractRecent work on the morality of hell spans the various subdisciplines of theology, with the ironic exception of theological ethics. An adequate defence of hell requires a positive account of how God's eternally tormenting some humans is beautiful, just and worthy of worship. This suggests a short-term and long-term task. The short-term task, which this article pursues, tests whether an adequate moral theory is available by evaluating three possible candidates, the third of which is the most interesting, as it offers a historicist defence of hell: we believe hell is cruel only because of aversions to cruel and unusual punishment that emerged in modernity. Nonetheless, all three defences are inadequate, suggesting a longer term goal: we need either better moral theories or better accounts of hell, as well as greater analytic clarity regarding theological statements of the form,I want doctrineyto be true but believe doctrinexis true.
Ultralow-power switching via defect engineering in germanium telluride phase-change memory devices
Authors: Nukala Pavan , Lin Chia-Chun , Composto Russell , Agarwal Ritesh 
Published: January 2016

AbstractCrystal–amorphous transformation achieved via the melt-quench pathway in phase-change memory involves fundamentally inefficient energy conversion events; and this translates to large switching current densities, responsible for chemical segregation and device degradation. Alternatively, introducing defects in the crystalline phase can engineer carrier localization effects enhancing carrier–lattice coupling; and this can efficiently extract work required to introduce bond distortions necessary for amorphization from input electrical energy. Here, by pre-inducing extended defects and thus carrier localization effects in crystalline GeTe via high-energy ion irradiation, we show tremendous improvement in amorphization current densities (0.13–0.6 MA cm−2) compared with the melt-quench strategy (∼50 MA cm−2). We show scaling behaviour and good reversibility on these devices, and explore several intermediate resistance states that are accessible during both amorphization and recrystallization pathways. Existence of multiple resistance states, along with ultralow-power switching and scaling capabilities, makes this approach promising in context of low-power memory and neuromorphic computation.
A systematic comparison of sugar content in low-fat vs regular versions of food
Authors: Nguyen P K , Lin S , Heidenreich P 
Published: January 2016

AbstractObesity remains a significant public health concern. One of the primary messages from providers and health-care organizations is to eat healthier foods with lower fat. Many in the lay press, however, have suggested that lower fat versions of foods contain more sugar. To our knowledge, a systematic comparison of the sugar content in food with lower fat alternatives has not been performed. In this study, we compared fat free, low fat and regular versions of the same foods using data collected from the USDA National Nutrient Database. We found that the amount of sugar is higher in the low fat (that is, reduced calorie, light, low fat) and non-fat than ‘regular’ versions of tested items (Friedman P=0.00001, Wilcoxon P=0.0002 for low fat vs regular food and P=0.0003 for non-fat vs regular food). Our data support the general belief that food that is lower in fat may contain more sugar.
Waveguide Characterization of S-Band Microwave Mantle Cloaks for Dielectric and Conducting Objects
Authors: Vitiello Antonino , Moccia Massimo , Papari Gian Paolo , D’Alterio Giuliana , Vitiello Roberto , Galdi Vincenzo , Andreone Antonello 
Published: January 2016

AbstractWe present the experimental characterization of mantle cloaks designed so as to minimize the electromagnetic scattering of moderately-sized dielectric and conducting cylinders at S-band microwave frequencies. Our experimental setup is based on a parallel-plate waveguide system, which emulates a two-dimensional plane-wave scattering scenario and allows the collection of near-field maps as well as more quantitative assessments in terms of global scattering observables (e.g., total scattering width). Our results, in fairly good agreement with full-wave numerical simulations, provide a further illustration of the mantle- cloak mechanism, including its frequency-sensitivity and confirm its effectiveness both in restoring the near-field impinging wavefront around the scatterer and in significantly reducing the overall scattering.
Experimental Observation of Bohr’s Nonlinear Fluidic Surface Oscillation
Authors: Moon Songky , Shin Younghoon , Kwak Hojeong , Yang Juhee , Lee Sang-Bum , Kim Soyun , An Kyungwon 
Published: January 2016

AbstractNiels Bohr in the early stage of his career developed a nonlinear theory of fluidic surface oscillation in order to study surface tension of liquids. His theory includes the nonlinear interaction between multipolar surface oscillation modes, surpassing the linear theory of Rayleigh and Lamb. It predicts a specific normalized magnitude of 0.416η2 for an octapolar component, nonlinearly induced by a quadrupolar one with a magnitude of η much less than unity. No experimental confirmation on this prediction has been reported. Nonetheless, accurate determination of multipolar components is important as in optical fiber spinning, film blowing and recently in optofluidic microcavities for ray and wave chaos studies and photonics applications. Here, we report experimental verification of his theory. By using optical forward diffraction, we measured the cross-sectional boundary profiles at extreme positions of a surface-oscillating liquid column ejected from a deformed microscopic orifice. We obtained a coefficient of 0.42 ± 0.08 consistently under various experimental conditions. We also measured the resonance mode spectrum of a two-dimensional cavity formed by the cross-sectional segment of the liquid jet. The observed spectra agree well with wave calculations assuming a coefficient of 0.414 ± 0.011. Our measurements establish the first experimental observation of Bohr’s hydrodynamic theory.
A framework for the assessment of the spatial and temporal patterns of threatened coastal delphinids
Authors: Wang Jingzhen , Yang Yingting , Yang Feng , Li Yuelin , Li Lianjie , Lin Derun , He Tangtian , Liang Bo , Zhang Tao , Lin Yao , Li Ping , Liu Wenhua 
Published: January 2016

AbstractThe massively accelerated biodiversity loss rate in the Anthropocene calls for an efficient and effective way to identify the spatial and temporal dynamics of endangered species. To this end, we developed a useful identification framework based on a case study of locally endangeredSousa chinensisby combining both LEK (local ecological knowledge) evaluation and regional boat-based survey methods. Our study investigated the basic ecological information ofSousa chinensisin the estuaries of eastern Guangdong that had previously been neglected, which could guide the future study and conservation. Based on the statistical testing of reported spatial and temporal dolphins sighting data from fishermen and the ecological monitoring analyses, including sighting rate, site fidelity and residence time estimations, some of the currentSousa chinensisunits are likely to be geographically isolated and critically endangered, which calls for much greater conservation efforts. Given the accelerated population extinction rate and increasing budgetary constraints, our survey pattern can be applied in a timely and economically acceptable manner to the spatial and temporal assessment of other threatened coastal delphinids, particularly when population distributions are on a large scale and traditional sampling methods are difficult to implement.
The lipidome associated with the γ-secretase complex is required for its integrity and activity
Authors: Ayciriex Sophie , Gerber Hermeto , Osuna Guillermo M. Garcia , Chami Mohamed , Stahlberg Henning , Shevchenko Andrej , Fraering Patrick C. 
Published: January 2016

γ-Secretase is a multi-subunit membrane protease complex that catalyses the final intramembrane cleavage of the β-amyloid precursor protein (APP) during the neuronal production of amyloid-β peptides (Aβ), which are implicated as the causative agents of Alzheimer's disease (AD). In the present study, we report the reconstitution of a highly purified, active γ-secretase complex into proteoliposomes without exogenous lipids and provide the first direct evidence for the existence of a microenvironment of 53 molecular species from 11 major lipid classes specifically associated with the γ-secretase complex, including phosphatidylcholine and cholesterol. Importantly, we demonstrate that the pharmacological modulation of certain phospholipids abolishes both the integrity and the enzymatic activity of the intramembrane protease. Together, our findings highlight the importance of a specific lipid microenvironment for the structure and function of γ-secretase.