bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of the multimeric structure of poly(A)-binding protein on a poly(A) tail
Authors: Sawazaki Ryoichi , Imai Shunsuke , Yokogawa Mariko , Hosoda Nao , Hoshino Shin-ichi , Mio Muneyo , Mio Kazuhiro , Shimada Ichio , Osawa Masanori 
Published: January 2018

AbstractEukaryotic mature mRNAs possess a poly adenylate tail (poly(A)), to which multiple molecules of poly(A)-binding protein C1 (PABPC1) bind. PABPC1 regulates translation and mRNA metabolism by binding to regulatory proteins. To understand functional mechanism of the regulatory proteins, it is necessary to reveal how multiple molecules of PABPC1 exist on poly(A). Here, we characterize the structure of the multiple molecules of PABPC1 on poly(A), by using transmission electron microscopy (TEM), chemical cross-linking, and NMR spectroscopy. The TEM images and chemical cross-linking results indicate that multiple PABPC1 molecules form a wormlike structure in the PABPC1-poly(A) complex, in which the PABPC1 molecules are linearly arrayed. NMR and cross-linking analyses indicate that PABPC1 forms a multimer by binding to the neighbouring PABPC1 molecules via interactions between the RNA recognition motif (RRM) 2 in one molecule and the middle portion of the linker region of another molecule. A PABPC1 mutant lacking the interaction site in the linker, which possesses an impaired ability to form the multimer, reduced the in vitro translation activity, suggesting the importance of PABPC1 multimer formation in the translation process. We therefore propose a model of the PABPC1 multimer that provides clues to comprehensively understand the regulation mechanism of mRNA translation.
New rapid one-step PCR diagnostic assay for Plasmodium falciparum infective mosquitoes
Authors: Kefi Mary , Mavridis Konstantinos , Simões Maria L. , Dimopoulos George , Siden-Kiamos Inga , Vontas John 
Published: January 2018

AbstractAn essential component of malaria vector control programmes is the detection of Plasmodium falciparum within its mosquito vectors, particularly in the salivary glands where the infective sporozoites reside. Several protocols have been developed for this purpose; however they require dissection of mosquito specimens prior to analysis. Here, a novel one-step RT-qPCR TaqMan diagnostic assay was developed for mosquitoes with infective Plasmodium falciparum sporozoites in the salivary glands. It is based on detection of the sporozoite-specific Pfslarp and Pfplp1 gene transcripts. These transcripts were chosen based on bioinformatics analysis, and experimentally verified to be overexpressed in the salivary gland sporozoite stage of the parasite compared to other mosquito parasite stages. The proof of principle and the performance of the assay were demonstrated using RNAlater preserved mosquito samples. Tests of analytical sensitivity showed the novel TaqMan assay to be 100% accurate, although its performance in the field needs to be further demonstrated. This method has no requirement for dissection and post-PCR processing and thus is simple and rapid to perform in individual mosquitoes or mosquito pools. It can be used in single or multiplex formats also targeting additional markers expressed in different tissues, such as detoxification enzymes associated with insecticide resistance.
Effect of Salt Intake on Plasma and Urinary Uric Acid Levels in Chinese Adults: An Interventional Trial
Authors: Wang Yang , Chu Chao , Wang Ke-Ke , Hu Jia-Wen , Yan Yu , Lv Yong-Bo , Cao Yu-Meng , Zheng Wen-Ling , Dang Xi-Long , Xu Jing-Tao , Chen Wei , Yuan Zu-Yi , Mu Jian-Jun 
Published: January 2018

AbstractUric acid (UA) has been proposed as an important risk factor for cardiovascular and renal morbidity. We conducted an interventional trial to assess effects of altered salt intake on plasma and urine UA levels and the relationship between UA levels and salt sensitivity in humans. Ninety subjects (18–65 years old) were sequentially maintained on a normal diet for 3 days at baseline, a low-salt diet for 7 days (3.0 g/day, NaCl), and a high-salt diet for an additional 7 days (18.0 g/day of NaCl). Plasma UA levels significantly increased from baseline to low-salt diet and decreased from low-salt to high-salt diet. By contrast, daily urinary levels of UA significantly decreased from baseline to low-salt diet and increased from low-salt to high-salt diet. The 24 h urinary sodium excretions showed inverse correlation with plasma UA and positive correlation with urinary UA excretions. Additionally, salt-sensitive subjects presented significantly higher plasma UA changes in comparison to salt-resistant subjects, and a negative correlation was observed between degree of salt sensitivity and plasma UA difference. The present study indicates that variations in dietary salt intake affect plasma and urine UA levels, and plasma UA may be involved in pathophysiological process of salt sensitivity.
Vasodilator-stimulated phosphoprotein promotes liver metastasis of gastrointestinal cancer by activating a β1-integrin-FAK-YAP1/TAZ signaling pathway
Authors: Xiang Xiaoyu , Wang Yuanguo , Zhang Hongbin , Piao Jinhua , Muthusamy Selvaraj , Wang Lei , Deng Yibin , Zhang Wei , Kuang Rui , Billadeau Daniel D. , Huang Shengbing , Lai Jinping , Urrutia Raul , Kang Ningling 
Published: January 2018

AbstractExtracellular matrix (ECM)-induced β1-integrin-FAK signaling promotes cell attachment, survival, and migration of cancer cells in a distant organ so as to enable cancer metastasis. However, mechanisms governing activation of the β1-integrin-FAK signaling remain incompletely understood. Here, we report that vasodilator-stimulated phosphoprotein (VASP), an actin binding protein, is required for ECM–mediated β1-integrin-FAK-YAP1/TAZ signaling in gastrointestinal (GI) cancer cells and their liver metastasis. In patient-derived samples, VASP is upregulated in 53 of 63 colorectal cancers and 43 of 53 pancreatic ductal adenocarcinomas and high VASP levels correlate with liver metastasis and reduced patient survival. In a Matrigel-based 3-dimensional (3D) culture model, short hairpin RNA (shRNA)–mediated VASP knockdown in colorectal cancer cells (KM12L4, HCT116, and HT29) and pancreatic cancer cells (L3.6 and MIA PaCa-1) suppresses the growth of 3D cancer spheroids. Mechanistic studies reveal that VASP knockdown suppresses FAK phosphorylation and YAP1/TAZ protein levels, but not Akt or Erk-related pathways and that YAP1/TAZ proteins are enhanced by the β1-integrin-FAK signaling. Additionally, VASP regulates the β1-integrin-FAK-YAP1/TAZ signaling by at least two mechanisms: (1) promoting ECM-mediated β1-integrin activation and (2) regulating YAP1/TAZ dephosphorylation at downstream of RhoA to enhance the stability of YAP1/TAZ proteins. In agreement with these, preclinical studies with two experimental liver metastasis mouse models demonstrate that VASP knockdown suppresses GI cancer liver metastasis, β1-integrin activation, and YAP1/TAZ levels of metastatic cancer cells. Together, our data support VASP as a treatment target for liver metastasis of colorectal and pancreatic cancers.
Methanol ice co-desorption as a mechanism to explain cold methanol in the gas-phase
Authors: Ligterink N. F. W. , Walsh C. , Bhuin R. G. , Vissapragada S. , Terwisscha van Scheltinga J. , Linnartz H. 
Published: January 2018

Context. Methanol is formed via surface reactions on icy dust grains. Methanol is also detected in the gas-phase at temperatures below its thermal desorption temperature and at levels higher than can be explained by pure gas-phase chemistry. The process that controls the transition from solid state to gas-phase methanol in cold environments is not understood.
Aims. The goal of this work is to investigate whether thermal CO desorption provides an indirect pathway for methanol to co-desorb at low temperatures.
Methods. Mixed CH3OH:CO/CH4 ices were heated under ultra-high vacuum conditions and ice contents are traced using RAIRS (reflection absorption IR spectroscopy), while desorbing species were detected mass spectrometrically. An updated gas-grain chemical network was used to test the impact of the results of these experiments. The physical model used is applicable for TW Hya, a protoplanetary disk in which cold gas-phase methanol has recently been detected.
Results. Methanol release together with thermal CO desorption is found to be an ineffective process in the experiments, resulting in an upper limit of ≤ 7.3 × 10−7 CH3OH molecules per CO molecule over all ice mixtures considered. Chemical modelling based on the upper limits shows that co-desorption rates as low as 10−6 CH3OH molecules per CO molecule are high enough to release substantial amounts of methanol to the gas-phase at and around the location of the CO thermal desorption front in a protoplanetary disk. The impact of thermal co-desorption of CH3OH with CO as a grain-gas bridge mechanism is compared with that of UV induced photodesorption and chemisorption.
Knochenstoffwechsel im Alter
Authors: Rolvien Tim , Amling Michael 
Published: January 2018

ZusammenfassungDas Skelettsystem wird unter optimalen Bedingungen lebenslang erneuert, um sich mechanischen Belastungen anpassen sowie Knochenbrüchen Widerstand leisten zu können. Mit dem Alter kann sich das Gleichgewicht zwischen Knochenauf- und -abbau auf die Seite des Abbaus verschieben sowie die Knochenqualität verschlechtern, was zu einem Anstieg des Frakturrisikos führt. Ursächlich hierfür sind u. a. die Abnahme der regenerativen Kapazität mesenchymaler Stammzellen und die dadurch verminderte Knochenformation durch Osteoblasten. Des Weiteren sinkt die Zahl der sich im Knochen befindenden Osteozyten und es kommt zu zellintrinsischen Prozessen wie einer Anhäufung von reaktiven Sauerstoffspezies sowie verminderter lysosomaler Verdauung (Autophagozytose). Der Mangel an Geschlechtshormononen, Wachstumsfaktoren sowie endogener Glukokortikoidüberschuss und fehlende körperliche Bewegung sind weitere Faktoren, die im Alter zu einem katabolen Knochenstoffwechsel und einer Abnahme der Knochenmasse führen können. Patienten nach erfolgter Fraktur und über 60 Jahren sollten daher vor allem bei Vorhandensein von typischen Risikofaktoren osteologisch untersucht werden. Zur osteologischen Basisdiagnostik gehört die Knochendichtemessung in DXA-Technologie (DXA: dual-energy X-ray absorptiometry) und ein ausführliches osteologisches Labor inklusive Bestimmung von Vitamin D (25-Hydroxy-Vitamin-D3). Die Patienten, deren statistisches Frakturrisiko ein Level von 30% übersteigt, erhalten dann zusätzlich zur Basistherapie in Form von Bewegung und Vitamin-D-Substitution eine spezifische osteologische Therapie (wie z. B. Bisphosphonat, Denosumab, Teriparatid), was mit einer erheblichen Risikoreduktion für weitere Frakturen einhergeht. Zusammenfassend stellt das Lebensalter einen Hauptrisikofaktor für Knochenbrüche und Osteoporose dar, weshalb die entsprechenden Patienten richtig diagnostiziert und behandelt werden müssen. So können die meisten Frakturen verhindert werden.
Alterstraumatologie im Gesichtsschädelbereich
Authors: Cornelius Carl-Peter , Mast Gerson , Goetz Philipp , Ehrenfeld Michael , Metzger Marc-Christian , Probst Florian 
Published: January 2018

ZusammenfassungCMF-Traumen im Alter 65+ sind durch besondere Merkmale gekennzeichnet: Lokalisation und Frakturmuster, Stand des Involutionsprozesses mit Abnahme von Knochenquantität und -qualität, Begleitverletzungen, altersassoziierte physische und psychische Funktionseinbußen und präexistente Komorbiditäten. Der Stand des Wissens und aktuelle bevölkerungsbezogene Daten dieser Variablen werden zu Anfang dieser Übersicht dargestellt. Vor diesem Hintergrund wird dann zu den verschiedenen Frakturen und Frakturtypen in den einzelnen Regionen des Gesichtsschädelskeletts Stellung genommen und die Indikation zu einem konservativen oder operativen Prozedere in den Alterspopulationen diskutiert. Spezielle Aufmerksamkeit kommt dabei Fraktursituationen bei Zahnlosigkeit und Atrophie im Ober- und/oder Unterkiefer zu. Innerhalb des weitgesteckten Gesamtspektrums der Frakturszenarien haben schonende, situationsadaptierte, ggf. auch unkonventinelle Lösungen Priorität vor Standardtherapieverfahren. Neue Techniken wie computerassistierte Chirurgie und patientenspezifische Implantate spielen eine immer größere Rolle und werden an Einzelbeispielen demonstriert. Betont werden muss, dass die physischen Reserven und nötigenfalls die geriatrietypische Multimorbidität jedes Patienten individuell einzuschätzen ist und vorrangige Bedeutung vor dem kalendarischen Lebensalter hat.
Phenolic Compounds as Arginase Inhibitors: New Insights Regarding Endothelial Dysfunction Treatment
Authors: Minozzo Bruno , Fernandes Daniel , Beltrame Flávio 
Published: January 2018

AbstractEndothelial dysfunction is characterised by the low bioavailability of nitric oxide with a relevant negative impact on the nitric oxide/cGMP pathway. The loss of nitric oxide/cGMP signaling may be caused by an increased arginase activity. Plant-derived substances, especially polyphenols, are compounds that have the potential to inhibit arginase activity and they may represent an attractive therapeutic option to combat clinical outcomes related to endothelial dysfunction. An extensive review was carried out using all available data published in English in the Pubmed database, and without restriction regarding the year of publication. Despite the increased number of new substances that have been tested as arginase inhibitors, it is rare to find a compound that satisfies all the toxicological criteria to be used in the development of a new drug. On the other hand, recent data have shown that substances from plants have great potential to be applied as arginase inhibitors, most of which are polyphenols. Of the relevant mechanisms in this process, the inhibition of arginase by natural products seems to act against endothelial dysfunction by reestablishing the vascular function and elevating nitric oxide levels (by increasing the amounts of substrate (L-arginine, and endothelial nitric oxide synthase activation and stabilisation) as well as decreasing the generation of reactive species (formed by uncoupledendothelial nitric oxide synthase). This review summarises several topics regarding arginase inhibition by natural substances as well as indicating this pathway as an emergent strategy to elevate nitric oxide levels in disorders involving endothelial dysfunction. In addition, some aspects regarding structural activity and future perspectives are discussed.
On the folding of a structurally complex protein to its metastable active state
Authors: Giri Rao V. V. Hemanth , Gosavi Shachi 
Published: January 2018

Significance
Proteins usually fold to their thermodynamically stable states. The serine protease inhibitors (serpins) modulate several biological processes such as blood clotting and inflammation. These proteins are unusual because their functionally active state, and consequently the state that they need to fold to and populate, is significantly less stable than an alternate latent conformation. This metastability facilitates conformational conversion to the inactive state which irreversibly traps the protease. However, it also makes the serpins prone to disease-linked polymerization. Here, we investigate the structural basis for this conformational choice using folding simulations of the serpin, α1-antitrypsin. We find that the structure of the protease-binding reactive center loop is determined early during folding and gates kinetic accessibility to the latent conformation.
Role of boundary conditions in determining cell alignment in response to stretch
Authors: Chen Kellen , Vigliotti Andrea , Bacca Mattia , McMeeking Robert M. , Deshpande Vikram S. , Holmes Jeffrey W. 
Published: January 2018

Significance
Alignment of cells in response to mechanical cues plays an important role in a wide range of physiologic processes. Multiple cell types orient perpendicular to applied cyclic stretch in 2D culture but parallel to stretch in 3D culture, and the mechanisms underlying this behavior remain elusive. We tested a promising hypothesized mechanism called strain avoidance and showed that it cannot explain cell alignment across the conditions that we examined. By contrast, a computational model of stress fiber kinetics incorporating the influence of traction boundary conditions and altered strain transmission in soft gels reproduced all of our experimental results as well as published 2D stretch experiments. These findings could improve understanding, modeling, and therapeutic modulation of tissue development, regeneration, and repair.
Functional evolution of biosynthetic enzymes that produce plant volatiles*
Authors: Koeduka Takao 
Published: January 2018

AbstractPlants synthesize volatile compounds to attract pollinators. The volatiles emitted by flowers are often complex mixtures of organic compounds; pollinators are capable of distinctly recognizing different volatile compounds. Plants also produce volatile compounds to protect themselves against herbivores and pathogens. Some of the volatile compounds produced in floral and vegetative tissues are toxic to insects and microbes. To adapt changes in the environment, plants have evolved the ability to synthesize a unique set of volatiles. Intensive studies have identified and characterized the enzymes responsible for the formation of plant volatiles. In particular, many biosynthetic genes have been isolated and their enzymatic functions have been proposed. This review describes how plants have evolved the biosynthetic pathways leading to the formation of green leaf volatiles and phenylpropene volatiles.
Central banking and the infrastructural power of finance: the case of ECB support for repo and securitization markets
Authors: Braun Benjamin 
Published: January 2018

Abstract
The pre-crisis rise and post-crisis resilience of European repo and securitization markets represent political victories for the interests of large banks. To explain when and how finance wins, the literature emphasizes lobbying capacity (instrumental power) and the financial sector’s central position in the economy (structural power). Increasingly, however, finance also enjoys infrastructural power, which stems from entanglements between specific financial markets and public-sector actors, such as treasuries and central banks, which govern by transacting in those markets. To demonstrate the analytical value of this perspective, the article traces how the European Central Bank (ECB), motivated by monetary policy considerations, has shaped post-crisis financial policymaking in the EU. It shows that the ECB has played a key part in fending off a financial transaction tax on repos and in shoring up and rebuilding the securitization market. With market-based forms of state agency on the rise, infrastructural entanglement and power shed new light on the politics of finance.
Extended Versus Intermittent Infusions of Cefepime for the Treatment of Febrile Neutropenia
Authors: Przybylski Daniel J. , Reeves David J. 
Published: January 2018

Background
Neutropenic fever is an oncologic emergency treated with β-lactam antibiotics. Previous literature suggests that extended infusions of β-lactam antibiotics may improve clinical outcomes. Currently, there is only 1 previous study investigating the use of extended infusions in this population, which demonstrated a lack of benefit.

Objective
The objective of this study was to determine the effectiveness of extended infusions of cefepime compared with intermittent infusions in patients with febrile neutropenia.

Methods
A retrospective chart review was completed comparing extended infusions with intermittent infusions of cefepime for febrile neutropenia. Adult patients admitted to a community teaching hospital who incurred febrile neutropenia were included.

Results
A total of 166 patients receiving cefepime were included, of which 28 received extended infusions and 138 received intermittent infusions. Overall, baseline characteristics were similar between groups besides receipt of prior chemotherapy, duration of neutropenia, optimal renal dosing, and presence of documented mucositis. In the extended infusion arm, defervescence at 24 hours was more frequent (82% vs 51%, P = 0.002) and median time to defervescence was decreased by 14 hours (10 vs 24 hours, P = 0.02). Furthermore, extended infusions increased the odds of defervescence at 24 hours by 4.28 (95% confidence interval, 1.43–12.75; P = 0.009) and doubled the likelihood of defervescence at any time (hazard ratio, 2.02; 95% confidence interval, 1.23–3.32, P = 0.005).

Conclusions
Contrary to prior literature, extended infusions of cefepime significantly decreased the time to defervescence and increased the proportion with defervescence at 24 hours. This suggests that extended infusions of cefepime may be superior to intermittent infusions, but future prospective studies are needed to confirm these findings.
An Innovative Solution for Prolonged Air Leaks
Authors: Mehta Ravindra M. , Singla Abhinav , Bhat Rajani S. , Godara Rakesh , Lokanath Chakravarthi , Cutaia Michael 
Published: January 2018

Background:
Prolonged air leak (PAL) is a life-threatening condition that can present either as bronchopleural fistula, or alveolar-pleural fistula (APF). Although numerous bronchoscopic treatments are described, they are either expensive, not widely available in the developing world or have limited success. We describe our experience with a novel customized endobronchial silicone blocker (CESB) for PAL treatment.

Methods:
This is a retrospective study of PAL patients who underwent CESB placement. The air leak was localized using a balloon occlusion test. The CESB was uniquely designed by molding silicone stent pieces into a conical shape, deployed with rigid bronchoscopy into the appropriate segment, and reinforced with cyanoacrylate glue to prevent migration. In patients with APF, pleurodesis was performed after leak resolution to prevent recurrence. Following this, the CESB was removed after 6 weeks.

Results:
Forty-nine CESBs were placed in 31 patients (25 male individuals, 6 female individuals) with mean age of 49.7±19.7 years. The PALs included APF (n=16), bronchopleural fistula (n=14), and airway-mediastinal fistula (n=1). The average diameter of the CESB used was 7.9±2.9 mm. There was resolution of the PAL in 26 of 31 patients (84%). The CESB migrated in 5 patients with no adverse events. Pleurodesis was performed in 13 of 16 patients with APF, to prevent recurrence. No other significant complications were observed.

Conclusions:
CESBs represent a safe, effective, and innovative approach in the management of PAL. They should be considered in patients who are not surgical candidates, fail surgery, or those who have a recurrence following surgery.