bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sphingolipids inhibit vimentin-dependent cell migration
Authors: Hyder Claire L. , Kemppainen Kati , Isoniemi Kimmo O. , Imanishi Susumu Y. , Goto Hidemasa , Inagaki Masaki , Fazeli Elnaz , Eriksson John E. , Törnquist Kid 
Published: April 2015

ABSTRACT
The sphingolipids, sphingosine 1-phosphate (S1P) and sphingosylphosphorylcholine (SPC), can induce or inhibit cellular migration. The intermediate filament protein vimentin is an inducer of migration and a marker for epithelial–mesenchymal transition. Given that keratin intermediate filaments are regulated by SPC, with consequences for cell motility, we wanted to determine whether vimentin is also regulated by sphingolipid signalling and whether it is a determinant for sphingolipid-mediated functions. In cancer cells where S1P and SPC inhibited migration, we observed that S1P and SPC induced phosphorylation of vimentin on S71, leading to a corresponding reorganization of vimentin filaments. These effects were sphingolipid-signalling-dependent, because inhibition of either the S1P2 receptor (also known as S1PR2) or its downstream effector Rho-associated kinase (ROCK, for which there are two isoforms ROCK1 and ROCK2) nullified the sphingolipid-induced effects on vimentin organization and S71 phosphorylation. Furthermore, the anti-migratory effect of S1P and SPC could be prevented by expressing S71-phosphorylation-deficient vimentin. In addition, we demonstrated, by using wild-type and vimentin-knockout mouse embryonic fibroblasts, that the sphingolipid-mediated inhibition of migration is dependent on vimentin. These results imply that this newly discovered sphingolipid–vimentin signalling axis exerts brake-and-throttle functions in the regulation of cell migration.
SUMOylation regulates ciliary localization of olfactory signaling proteins
Authors: McIntyre Jeremy C. , Joiner Ariell M. , Zhang Lian , Iñiguez-Lluhí Jorge , Martens Jeffrey R. 
Published: April 2015

ABSTRACTCilia are evolutionarily conserved organelles found on many mammalian cell types, including neuronal populations. Although neuronal cilia, including those on olfactory sensory neurons (OSNs), are often delineated by localization of adenylyl cyclase 3 (AC3, also known as ADCY3), the mechanisms responsible for targeting integral membrane proteins are largely unknown. Post-translational modification by small ubiquitin-like modifier (SUMO) proteins plays an important role in protein localization processes such as nuclear–cytosolic transport. Here, we identified through bioinformatic analysis that adenylyl cyclases harbor conserved SUMOylation motifs, and show that AC3 is a substrate for SUMO modification. Functionally, overexpression of the SUMO protease SENP2 prevented ciliary localization of AC3, without affecting ciliation or cilia maintenance. Furthermore, AC3-SUMO mutants did not localize to cilia. To test whether SUMOylation is sufficient for cilia entry, we compared localization of ANO2, which possesses a SUMO motif, and ANO1, which lacks SUMOylation sites and does not localize to cilia. Introduction of SUMOylation sites into ANO1 was not sufficient for ciliary entry. These data suggest that SUMOylation is necessary but not sufficient for ciliary trafficking of select constituents, further establishing the link between ciliary and nuclear import.
Protection ofDrosophilachromosome ends through minimal telomere capping
Authors: Dubruille Raphaëlle , Loppin Benjamin 
Published: April 2015

ABSTRACTIn Drosophila, telomere-capping proteins have the remarkable capacity to recognize chromosome ends in a sequence-independent manner. This epigenetic protection is essential to prevent catastrophic ligations of chromosome extremities. Interestingly, capping proteins occupy a large telomere chromatin domain of several kilobases; however, the functional relevance of this to end protection is unknown. Here, we investigate the role of the large capping domain by manipulating HOAP (encoded by caravaggio) capping-protein expression in the male germ cells, where telomere protection can be challenged without compromising viability. We show that the exhaustion of HOAP results in a dramatic reduction of other capping proteins at telomeres, including K81 [encoded by ms(3)K81], which is essential for male fertility. Strikingly however, we demonstrate that, although capping complexes are barely detected in HOAP-depleted male germ cells, telomere protection and male fertility are not dramatically affected. Our study thus demonstrates that efficient protection of Drosophila telomeres can be achieved with surprisingly low amounts of capping complexes. We propose that these complexes prevent fusions by acting at the very extremity of chromosomes, reminiscent of the protection conferred by extremely short telomeric arrays in yeast or mammalian systems.
GSTO1-1 modulates metabolism in macrophages activated through the LPS and TLR4 pathway
Authors: Menon Deepthi , Coll Rebecca , O'Neill Luke A. J. , Board Philip G. 
Published: April 2015

ABSTRACT
Macrophages mediate innate immune responses that recognise foreign pathogens, and bacterial lipopolysaccharide (LPS) recruits a signalling pathway through Toll-like receptor 4 (TLR4) to induce pro-inflammatory cytokines and reactive oxygen species (ROS). LPS activation also skews the metabolism of macrophages towards a glycolytic phenotype. Here, we demonstrate that the LPS-triggered glycolytic switch is significantly attenuated in macrophages deficient for glutathione transferase omega-1 (GSTO1, note that GSTO1-1 refers to the dimeric molecule with identical type 1 subunits). In response to LPS, GSTO1-1-deficient macrophages do not produce excess lactate, or dephosphorylate AMPK, a key metabolic stress regulator. In addition, GSTO1-1-deficient cells do not induce HIF1α, which plays a key role in maintaining the pro-inflammatory state of activated macrophages. The accumulation of the TCA cycle intermediates succinate and fumarate that occurs in LPS-treated macrophages was also blocked in GSTO1-1-deficient cells. These data indicate that GSTO1-1 is required for LPS-mediated signalling in macrophages and that it acts early in the LPS–TLR4 pro-inflammatory pathway.
Inhibiting IκBβ–NFκB signaling attenuates the expression of select pro-inflammatory genes
Authors: McKenna Sarah , Wright Clyde J. 
Published: April 2015

ABSTRACTMultiple mediators of septic shock are regulated by the transcription factor nuclear factor κB (NFκB). However, complete NFκB inhibition can exacerbate disease, necessitating evaluation of targeted strategies to attenuate the pro-inflammatory response. Here, we demonstrate that in murine macrophages, low-dose NFκB inhibitors specifically attenuates lipopolysaccharide (LPS)-induced IκBβ degradation and the expression of a select subset of target genes (encoding IL1β, IL6, IL12β). Gain- and loss-of-function experiments demonstrate the necessary and sufficient role of inhibitor of NFκB family member IκBβ (also known as NFKBIB) in the expression of these genes. Furthermore, both fibroblasts and macrophages isolated from IκBβ overexpressing mice demonstrate attenuated LPS-induced IκBβ–NFκB signaling and IL1β, IL6 and IL12β expression. Further confirming the role of IκBβ and its NFκB subunit binding partner cRel in LPS-induced gene expression, pre-treatment of wild-type mouse embryonic fibroblasts with a cell-permeable peptide containing the cRel nuclear localization sequence attenuated IL6 expression. We prove that LPS-induced IκBβ–NFκB signaling can be selectively modulated to attenuate the expression of select pro-inflammatory target genes, thus providing therapeutic insights for patients exposed to systemic inflammatory stress.
The P2Y2 receptor promotes Wnt3a- and EGF-induced epithelial tubular formation by IEC6 cells by binding to integrins
Authors: Ibuka Souji , Matsumoto Shinji , Fujii Shinsuke , Kikuchi Akira 
Published: April 2015

ABSTRACT
Epithelial tubular structures are essential units in various organs. Here, we used rat intestinal epithelial IEC6 cells to investigate tubulogenesis and we found that tubular formation was induced by a combination of Wnt3a and EGF signaling during three-dimensional culture. Wnt3a and EGF induced the expression of the P2Y2 receptor (P2Y2R, also known as P2RY2), and knockdown of P2Y2R suppressed tubular formation. A P2Y2R mutant that lacks nucleotide responsiveness rescued the phenotypes resulting from P2Y2R knockdown, suggesting that nucleotide-dependent responses are not required for P2Y2R functions in tubular formation. The Arg-Gly-Asp (RGD) sequence of P2Y2R has been shown to interact with integrins, and a P2Y2R mutant lacking integrin-binding activity was unable to induce tubular formation. P2Y2R expression inhibited the interaction between integrins and fibronectin, and induced cell morphological changes and proliferation. Inhibition of integrin and fibronectin binding by treatment with the cyclic RGD peptide and fibronectin knockdown induced tubular formation in the presence of EGF alone, but a fibronectin coat suppressed Wnt3a- and EGF-induced tubular formation. These results suggest that Wnt3a- and EGF-induced P2Y2R expression causes tubular formation by preventing the binding of integrins and fibronectin rather than by mediating nucleotide responses.
The cost of digestion in the fish-eating myotis (Myotis vivesi)
Authors: Welch Kenneth C. , Otálora-Ardila Aída , Herrera M. L. Gerardo , Flores-Martínez José Juan 
Published: April 2015

ABSTRACTFlying vertebrates, such as bats, face special challenges with regards to the throughput and digestion of food. On the one hand, as potentially energy-limited organisms, bats must ingest and assimilate energy efficiently in order to satisfy high resting and active metabolic demands. On the other hand, the assimilation of nutrients must be accomplished using a digestive tract that is, compared with that of similarly sized non-flying vertebrates, significantly shorter. Despite these competing demands, and the relative breadth of dietary diversity among bats, little work has been done describing the cost of digestion, termed ‘specific dynamic action’ (SDA). Here, we provide the first systematic assessment of the SDA response in a bat, the fish-eating myotis (Myotis vivesi). Given the shorter digestive tract and the relatively higher resting and active metabolic rates of bats in general, and based on anecdotal published evidence, we hypothesized that the SDA response in fish-eating myotis would be dependent on meal size and both significantly more brief and intense than in small, non-flying mammals. In agreement with our hypothesis, we found that the peak metabolic rate during digestion, relative to rest, was significantly higher in these bats compared with any other mammals or vertebrates, except for some infrequently eating reptiles and amphibians. Additionally, we found that the magnitude and duration of the SDA response were related to meal size. However, we found that the duration of the SDA response, while generally similar to reported gut transit times in other small bats, was not substantially shorter than in similarly sized non-flying mammals.
A meta-analysis ofin vivovertebrate cardiac performance: implications for cardiovascular support in the evolution of endothermy
Authors: Hillman Stanley S. , Hedrick Michael S. 
Published: April 2015

ABSTRACTEndothermy in birds and mammals is associated with high body temperatures, and high rates of metabolism that are aerobically supported by elevated rates of cardiovascular O2 transport. The purpose of this meta-analysis was to examine cardiovascular data from ectothermic and endothermic vertebrates, at rest and during exercise, with the goal of identifying key variables that may have contributed to the role of the cardiovascular system in supporting high rates of O2 transport associated with endothermy. Vascular conductance, cardiac power and stroke work were summarized and calculated from a variety of studies at rest and during exercise for five classes of vertebrates where data were available. Conductance and cardiac power were linearly related to cardiac output from rest to exercise and also interspecifically. Exercise cardiac power and stroke work were greater in the endothermic species, owing to increased flow resulting from increased heart rate and increased pressure. Increased relative ventricle mass (RVM) was related to increased stroke volume in both groups. However, the increased RVM of endotherms was related to the increased pressure, as stroke work per gram of ventricle during exercise was equivalent between the groups. Cardiac power was linearly related to aerobic metabolic power, with 158 mW aerobic power output achieved per mW of cardiac power input. This analysis indicates that the greatly increased heart rate and cardiac stroke work leading to increased blood flow rate and blood pressure was necessary to support the metabolic requirements of endothermy.
Western and Clark's grebes use novel strategies for running on water
Authors: Clifton Glenna T. , Hedrick Tyson L. , Biewener Andrew A. 
Published: April 2015

ABSTRACTFew vertebrates run on water. The largest animals to accomplish this feat are western and Clark's grebes (Aechmophorus occidentalis and Aechmophorus clarkii). These birds use water running to secure a mate during a display called rushing. Grebes weigh an order of magnitude more than the next largest water runners, basilisk lizards (Basilicus basiliscus), and therefore face a greater challenge to support their body weight. How do these birds produce the hydrodynamic forces necessary to overcome gravity and sustain rushing? We present the first quantitative study of water running by grebes. High-speed video recordings elucidate the hindlimb movements of grebes rushing in the wild. We complement these findings with laboratory experiments using physical models and a preserved grebe foot to estimate how slapping the water surface contributes to weight support. Our results indicate that grebes use three novel tactics to successfully run on water. First, rushing grebes use exceptionally high stride rates, reaching 10 Hz. Second, grebe foot size and high water impact speed allow grebes to generate up to 30–55% of the required weight support through water slap alone. Finally, flattened foot bones reduce downward drag, permitting grebes to retract each foot from the water laterally. Together, these mechanisms outline a water-running strategy qualitatively different from that of the only previously studied water runner, the basilisk lizard. The hydrodynamic specializations of rushing grebes could inform the design of biomimetic appendages. Furthermore, the mechanisms underlying this impressive display demonstrate that evolution can dramatically alter performance under sexual selection.
Recent Advances in Copper-mediated Direct Biaryl Coupling
Authors: Hirano Koji , Miura Masahiro 
Published: April 2015

Abstract
Copper salts and complexes have recently received significant attention as less expensive, abundant, and unique alternatives to noble transition-metal catalysts such as palladium, rhodium, and ruthenium, in the research field of C–H activation. This highlight review focuses on recent advances in copper-mediated biaryl coupling via aromatic C–H cleavage, and the scope and limitations are briefly summarized.
Funding source and primary outcome changes in clinical trials registered on ClinicalTrials.gov are associated with the reporting of a statistically significant primary outcome: a cross-sectional study
Authors: Ramagopalan Sreeram V , Skingsley Andrew P. , Handunnetthi Lahiru , Magnus Daniel , Klingel Michelle , Pakpoor Julia , Goldacre Ben 
Published: April 2015

Background: We and others have shown a significant proportion of interventional trials registered on ClinicalTrials.gov have their primary outcomes altered after the listed study start and completion dates. The objectives of this study were to investigate whether changes made to primary outcomes are associated with the likelihood of reporting a statistically significant primary outcome on ClinicalTrials.gov.Methods: A cross-sectional analysis of all interventional clinical trials registered on ClinicalTrials.gov as of 20 November 2014 was performed. The main outcome was any change made to the initially listed primary outcome and the time of the change in relation to the trial start and end date.Findings: 13,238 completed interventional trials were registered with ClinicalTrials.gov that also had study results posted on the website. 2555 (19.3%) had one or more statistically significant primary outcomes. Statistical analysis showed that registration year, funding source and primary outcome change after trial completion were associated with reporting a statistically significant primary outcome.Conclusions: Funding source and primary outcome change after trial completion are associated with a statistically significant primary outcome report on clinicaltrials.gov.
Algorithm for the anesthetic management of cesarean delivery in patients with unsatisfactory labor epidural analgesia
Authors: Vaida Sonia , Cattano Davide , Hurwitz Debra , Mets Berend 
Published: April 2015

The management of a patient presenting with unsatisfactory labor epidural analgesia poses a severe challenge for the anesthetist wanting to provide safe anesthetic care for a cesarean delivery. Early recognition of unsatisfactory labor analgesia allows for replacement of the epidural catheter. The decision to convert labor epidural analgesia to anesthesia for cesarean delivery is based on the urgency of the cesarean delivery, airway examination, and the existence of a residual sensory and motor block. We suggest an algorithm which is implemented in our department, based on the urgency of the cesarean delivery.
Linking patient outcome to high throughput protein expression data identifies novel regulators of colorectal adenocarcinoma aggressiveness
Authors: French Christi L. , Ye Fei , Revetta Frank , Zhang Bing , Coffey Robert J. , Washington M. Kay , Deane Natasha G. , Beauchamp R. Daniel , Weaver Alissa M. 
Published: April 2015

A key question in cancer systems biology is how to use molecular data to predict the biological behavior of tumors from individual patients. While genomics data have been heavily used, protein signaling data are more directly connected to biological phenotype and might predict cancer phenotypessuch as invasion, metastasis, and patient survival. In this study, we mined publicly available data for colorectal adenocarcinoma from the Cancer Genome Atlas and identified protein expression and signaling changes that are statistically associated with patient outcome. Our analysis identified a number of known and potentially new regulators of colorectal cancer. High levels of insulin growth factor binding protein 2 (IGFBP2) were associated with both recurrence and death, and this was validated by immunohistochemical staining of a tissue microarray for a secondary patient dataset. Interestingly, GATA binding protein 3 (GATA3) was the protein most frequently associated with death in our analysis, and GATA3 expression was significantly decreased in tumor samples from stage I-II deceased patients. Experimental studies using engineered colon cancer cell lines show that exogenous expression of GATA3 decreases three-dimensional colony growth and invasiveness of colon cancer cells but does not affect two-dimensional proliferation. These findings suggest that protein data are useful for biomarker discovery and identify GATA3 as a regulator of colorectal cancer aggressiveness.
Intercompany Auditing Standards «The Statements and Management’s Explanations»
Authors: Лосева  , Loseva N. 
Published: April 2015

This material is developed by the author internal auditing standards, designed to determine the order of the use of statements and explanations guide entity as audit
evidence, the procedure has been documented, as well as the actions of the auditor with management’s refusal to submit such statements and explanations.
Internal Audit on Small Enterprises
Authors: Шешукова  , Sheshukova T. , Береснева  , Beresneva A. 
Published: April 2015

The article considers concepts of internal audit and offers a new definition for the tem. The audit of small enterprises of Perm Krai was conducted; the method of
defining organizational structure of internal audit was developed. As a result of theoretical basis and empirical experience functions of the internal auditor are defined.
Key words: internal audit, small businesses, organizational structure.
“Making meaning”: Communication between sign language users without a shared language
Authors: Zeshan Ulrike 
Published: April 2015

AbstractIn a small group of deaf sign language users from different countries and with no shared language, the signers’ initial conversational interactions are investigated as they meet in pairs for the very first time. This case study allows for a unique insight into the initial stages of pidginisation and the conceptual processes involved. The participants use a wide range of linguistic and communicative resources, and it can be argued that they construct shared multilingual-multimodal cognitive spaces for the purpose of these conversations. This research explores the nature of these shared multilingual-multimodal spaces, how they are shaped by the signers in interaction, and how they can be understood in terms of conceptual blending. The research also focuses on the meta-linguistic skills that signers use in these multilingual-multimodal interactions to “make meaning”.
Measurement of ethylene production as a method for determining the optimum harvest date of ‘Jonagored’ apples
Authors: Łysiak Grzegorz 
Published: April 2015

ABSTRACT
The measurement of ethylene concentration in the apple core is considered a good method of determining OHD, but requires high accuracy and expensive equipment. The measurement of ethylene production seems to be a technologically easier method. During research conducted in the years 2003-2008, measurements of ethylene production were evaluated as a method for determining the harvest maturity of ‘Jonagored’ apples intended for storage. Measurements were carried out every 4-5 days starting a few weeks before the estimated harvest date. Apples were picked on four dates and after five months the loss of mass, firmness, TSS and TA was measured, the incidence of physiological disorders and fungal diseases was assessed and sensory tests were conducted to evaluate storability. Based on this evaluation it was determined which of those dates was OHD. After a period of low ethylene production, the production accelerated rapidly to reach an average level between 10.0 and 12.5 ppm kg-1 hr-1 on the OHD. Later, ethylene production rose still more sharply and quickly reached several dozens of ppm kg-1 hr-1. The accuracy of the new method was compared with other methods used to determine the maturity stage. The results obtained through the measurement of ethylene production showed the least deviation from the six-year average and only the results obtained using the Streif index method, which may be unreliable for some cultivars according to the literature, had a comparable margin of error.