bluuebunny/crossref_metadata_2025_split huggingface dataset:
Contribution of the two dsRBM motifs to the double‐stranded RNA binding and protein interactions of PACT
Authors: Chukwurah Evelyn , Willingham Victoria , Singh Madhurima , Castillo‐Azofeifa David , Patel Rekha C. 
Published: December 2017

AbstractPACT is a stress‐modulated activator of protein kinase PKR (protein kinase, RNA activated), which is involved in antiviral innate immune responses and stress‐induced apoptosis. Stress‐induced phosphorylation of PACT is essential for PACT's increased association with PKR leading to PKR activation, phosphorylation of translation initiation factor eIF2α, inhibition of protein synthesis, and apoptosis. PACT‐induced PKR activation is negatively regulated by TRBP (transactivation response element RNA‐binding protein), which dissociates from PACT after PACT phosphorylation in response to stress signals. The conserved double‐stranded RNA binding motifs (dsRBMs) in PKR, PACT, and TRBP mediate protein‐protein interactions, and the stress‐dependent phosphorylation of PACT changes the relative strengths of PKR‐PACT, PACT‐TRBP, and PACT‐PACT interactions to bring about a timely and transient PKR activation. This regulates the general kinetics as well as level of eIF2α phosphorylation, thereby influencing the cellular response to stress either as recovery and survival or elimination by apoptosis. In the present study, we evaluated the effect of specific mutations within PACT's two evolutionarily conserved dsRBMs on dsRNA‐binding, and protein‐protein interactions between PKR, PACT, and TRBP. Our data show that the two motifs contribute to varying extents in dsRNA binding, and protein interactions. These findings indicate that although the dsRBM motifs have high sequence conservation, their functional contribution in the context of the whole proteins needs to be determined by mutational analysis. Furthermore, using a PACT mutant that is deficient in PACT‐PACT interaction but competent for PACT‐PKR interaction, we demonstrate that PACT‐PACT interaction is essential for efficient PKR activation.
Phosphorylated Tyr142 β‐catenin localizes to centrosomes and is regulated by Syk
Authors: Bhardwaj Deepshikha , Náger Mireia , Visa Anna , Sallán Marta C. , Coopman Peter J. , Cantí Carles , Herreros Judit 
Published: December 2017

Abstractβ‐catenin is a central component of adherent junctions and a key effector of canonical Wnt signaling, in which dephosphorylated Ser/Thr β‐catenin regulates gene transcription. β‐catenin phosphorylation at Tyr142 (PTyr142 β‐catenin), which is induced by receptor and Src family Tyr kinases, represents a previously described β‐catenin switch from adhesive to migratory roles. In addition to classical β‐catenin roles, phosphorylated Ser/Thr β‐catenin and total β‐catenin were involved in centrosomal functions, including mitotic spindle formation and centrosome separation. Here we find that PTyr142 β‐catenin is present in centrosomes in non‐transformed and glioblastoma cells and that, in contrast to the Ser/Thr phosphorylated β‐catenin, PTyr142 β‐catenin centrosomal levels drop in mitosis. Furthermore, we show that the inhibitor of Spleen Tyrosine Kinase (Syk) piceatannol decreases centrosomal PTyr142 β‐catenin levels, indicating that Syk regulates centrosome PTyr142 β‐catenin. Our findings suggest that PTyr142 β‐catenin and Syk may regulate centrosomal cohesion. This study highlights the contribution of different phosphorylated β‐catenin forms to the cell and centrosome cycles.
Retracted: Effect of the Wnt/β‐catenin signaling pathway on apoptosis, migration, and invasion of transplanted hepatocellular carcinoma cells after transcatheter arterial chemoembolization in rats
Authors: Wang Bao‐Ming , Li Nuo 
Published: December 2017

AbstractThis study aims to investigate the influence of the Wnt/β‐catenin signaling pathway on apoptosis, migration, and invasion of transplanted hepatocellular carcinoma (HCC) cells after transcatheter arterial chemoembolization (TACE) in rat models. A total of 80 rats were grouped into sham, TACE, Wnt‐C59, and TACE + Wnt‐C59 groups (n = 20). Ten days after model establishment, 10 rats in each group were executed to perform pathological examination and follow‐up experiment, and the remaining 10 rats in each group were reared to observe the survival condition. RT‐qPCR and Western blotting were applied to determine the expressions of Wnt1, β‐catenin, cyclin D1, c‐met, vimentin, E‐cadherin, and vascular endothelial growth factor (VEGF). ELISA was performed to measure the serum alpha‐fetoprotein (AFP) content of rats. Flow cytometry was used to evaluate cell apoptosis rate and transwell assay to examine cell migration and invasion. Compared with the TACE group, the Wnt‐C59 and TACE + Wnt‐C59 groups showed increased apoptosis and survival time (the TACE + Wnt‐C59 group > the Wnt‐C59 group). Compared with the sham group, the TACE + Wnt‐C59 groups showed decreased cancer tissue weight and expressions of Wnt1, β‐catenin, cyclin D1, vimentin, c‐met, and VEGF, but increased E‐cadherin expression. Compared with the TACE group, the Wnt‐C59 and TACE + Wnt‐C59 groups showed decreased AFP level, migration, and invasion (the TACE + Wnt‐C59 group < the Wnt‐C59 group). These findings indicate inhibition of the Wnt/β‐catenin signaling pathway improves therapeutic effect on TACE via suppressing migration, invasion, and promoting apoptosis of transplanted HCC cells in rats.
The US Food and Drug Administration's tentative approval process and the global fight against HIV
Authors: Chahal Harinder Singh , Murray Jeffrey S , Shimer Martin , Capella Peter , Presto Ryan , Valdez Mary Lou , Lurie Peter G 
Published: December 2017

AbstractIntroductionIn 2004, the US government began to utilize the Food and Drug Administration's (USFDA) tentative approval process (tFDA) as a basis to determine which HIV drugs are appropriate to be purchased and used in resource‐constrained settings. This process permits products that are not approved for marketing in the US, including medicines with active patents or marketing restrictions in the US, to be purchased and distributed in resource‐constrained settings. Although the tFDA was originally intended to support the United States’ President's Emergency Plan for AIDS Relief (PEPFAR), the USFDA list has become a cornerstone of international HIV programmes that support procurement of ARVs, such as the World Health Organization and the Global Fund to Fight AIDS, Tuberculosis, and Malaria. Our objective in this article is to help the global HIV policy makers and implementers of HIV programmes better understand the benefits and limitations of the tFDA by providing an in‐depth review of the relevant legal and regulatory processes.DiscussionUSFDA's dedicated tFDA process for ARVs used by the PEPFAR programme has a wide impact globally; however, the implementation and the regulatory processes governing the programme have not been thoroughly described in the medical literature. This paper seeks to help stakeholders better understand the legal and regulatory aspects associated with review of ARVs under the tFDA by describing the following: (1) the tFDA and its importance to global ARV procurement; (2) the regulatory pathways for applications under tFDA for the PEPFAR programme, including modifications to applications, review timelines and costs; (3) the role of US patents, US marketing exclusivity rights, and the Medicines Patents Pool in tFDA; and (4) an overview of how applications for PEPFAR programme are processed through the USFDA. We also provide a case study of a new ARV, tenofovir alafenamide fumarate (TAF), not yet reviewed by USFDA for PEPFAR use.ConclusionsIn this paper, we describe the importance and implementation of USFDA's tentative approval process to review ARVs for resource‐constrained settings. We also highlight the impact of patents and exclusivities on review of HIV drugs under tFDA and illustrate the concepts using a new HIV drug as an example.
Glial source of nitric oxide in epileptogenesis: A target for disease modification in epilepsy
Authors: Sharma Shaunik , Puttachary Sreekanth , Thippeswamy Thimmasettappa 
Published: December 2017

AbstractEpileptogenesis is the process of developing an epileptic condition and/or its progression once it is established. The molecules that initiate, promote, and propagate remarkable changes in the brain during epileptogenesis are emerging as targets for prevention/treatment of epilepsy. Epileptogenesis is a continuous process that follows immediately after status epilepticus (SE) in animal models of acquired temporal lobe epilepsy (TLE). Both SE and epileptogenesis are potential therapeutic targets for the discovery of anticonvulsants and antiepileptogenic or disease‐modifying agents. For translational studies, SE targets are appropriate for screening anticonvulsive drugs prior to their advancement as therapeutic agents, while targets of epileptogenesis are relevant for identification and development of therapeutic agents that can either prevent or modify the disease or its onset. The acute seizure models do not reveal antiepileptogenic properties of anticonvulsive drugs. This review highlights the important components of epileptogenesis and the long‐term impact of intervening one of these components, nitric oxide (NO), in rat and mouse kainate models of TLE. NO is a putative pleotropic gaseous neurotransmitter and an important contributor of nitro‐oxidative stress that coexists with neuroinflammation and epileptogenesis. The long‐term impact of inhibiting the glial source of NO during early epileptogenesis in the rat model of TLE is reviewed. The importance of sex as a biological variable in disease modification strategies in epilepsy is also briefly discussed.
JCB to Infinity and Beyond: A Personal Recollection and Recommendation
Authors: Simonton Dean Keith 
Published: December 2017

AbstractThe author starts by narrating his personal experiences with the Journal of Creative Behavior. Although the author began publishing his creativity research in 1975, he did not submit his first manuscript until 1981, 14 years after JCB's founding—a manuscript that was finally published in 1983 without ever being formally accepted! The author then turns to the events leading up to his assumption of the journal's editorship in 1993, describing the editorial endeavor that lasted until 1999. He concludes by discussing the aftermath, including the tremendous growth in publication opportunities for creativity research. That proliferation then inspires the recommendation that JCB continue to be considered a principal vehicle for all creativity researchers.
Creative Thinking Processes: The Past and the Future
Authors: Mumford Michael D. , McIntosh Tristan 
Published: December 2017

AbstractFor more than one hundred years, students of creativity, including seminal efforts published in theJournal of Creative Behavior, have sought to identify the key processes people must execute to produce creative problem solutions. In recent years, we have seen a consensual model of key creative thinking processes being accepted by the field. In the present effort, we review the evidence bearing on the eight core processes proposed in this consensual model. Subsequently, directions for future research on creative thinking processes are discussed.
Land use dynamics derived from colluvial deposits and bogs in the Black Forest, Germany
Authors: Henkner Jessica , Ahlrichs Jan , Fischer Elske , Fuchs Markus , Knopf Thomas , Rösch Manfred , Scholten Thomas , Kühn Peter 
Published: December 2017

AbstractThe Black Forest is considered to be a rather unfavorable area, having a short vegetation period, low mean annual temperatures, high precipitation, and a pronounced relief. These conditions do not favor agricultural land use and thus it is widely accepted that people only began using the land intensively during the Middle Ages. In this integrated study 17 soil profiles, two peat bogs and a database of archaeological finds were used to reconstruct past land use impacts on the environment. AMS–14C datings of charcoals, luminescence datings of colluvial deposits, archaeological finds and pollen records indicate land use already during the Neolithic. This pre‐medieval land use might be related to seasonal settlements dominated by pastoralism and the use of wood or bedrock to build settlements and infrastructure or as energy supply. There is new evidence of human activity dating back to the Bronze and Iron Age, which is a discrepancy to the absence of archaeological finds in the direct vicinity of the studied sites. With the beginning of the Middle Ages land use practices changed, most likely with the expansion and intensification of agricultural land use, which coincides with the increasing use of natural resources in the Black Forest. Hence, the main phases of colluvial deposition date to the Middle Ages and Modern Times. Increased contents of As, Cr, Cu, Pb, or Zn in medieval colluvial deposits might indicate smelting or mining, even though there are no known archeological sites pointing to such activities nearby. Whereas the pattern of colluvial deposition in the southeastern Black Forest points to distinct, but local land use in pre‐medieval times and to intensified and widespread land use since the Middle Ages, thick and multi‐layered colluvial deposits indicate intensive land use in the neighboring Baar region since the Neolithic. The different land use patterns of these two regions originate from the rather favorable conditions for agriculture in terms of soils, climate, and topography in the Baar region compared to the unfavorable conditions in the Black Forest.
Tree age affects physicochemical, functional quality and storability of Amrapali mango (Mangifera indica L.) fruits
Authors: Meena Nirmal Kumar , Asrey Ram 
Published: December 2017

AbstractBACKGROUNDThe effect of tree age on physicochemical quality attributes and storage behaviour of Amrapali mango fruit was evaluated. Physiologically mature fruits were harvested from 6‐, 18‐ and 30‐year‐old trees and kept for ripening under ambient conditions (temperature 35 ± 3 °C, relative humidity 60 ± 5%). Observations were recorded at 3‐day intervals.RESULTSHighest total soluble solids and total sugars were found in the fruit sourced from 18‐year‐old trees. At the end of storage, least titratable acidity (0.17%) and higher carotenoids (10.86 mg 100 g−1) were found in 30‐year‐old tree fruits during the last day of storage. Highest total phenols (TP) (251.33 μg gallic acid g−1), antioxidant capacity (AC) (5.63 μmol Trolox g−1) and ascorbic acid (AA) (31.13 mg 100 g−1) were reported in fruits from younger trees of 6 years old. Maximum respiratory and ethylene evolution peak was observed in fruits obtained from oldest trees, whereas least activities of pectin methyl esterase (0.31 μmol min−1 g−1 fresh weight) and polygalacturonase (53.67 μg galacturonic acid g−1 h−1) were observed in 6‐year‐old tree fruits at the end of the 9‐day storage period.CONCLUSIONHigher total soluble solids and total sugars were found in fruit harvested from middle‐age‐group (18‐year‐old) trees during the entire storage period of 9 days. Most of the functional parameters, such as TP, AC and AA, were observed to be higher in fruits from younger (6‐year‐old) trees. The obtained results revealed that produce from middle‐age‐group (18‐year‐old) Amrapali mango orchards suit consumers' and processors' requirements. © 2017 Society of Chemical Industry
Interactive effects of dietary phosphorus and iron on Daphnia life history
Authors: Lind Patrick R. , Jeyasingh Punidan D. 
Published: December 2017

AbstractFood quality of freshwater consumers is often defined as the relative supply of carbon (C) to phosphorus (P) in diet. The growth rate hypothesis makes mechanistic links between P supply, ribosome biogenesis, and growth, with subsequent impacts on other life history traits such as age at maturity and clutch size. However, we know surprisingly little about the role and importance of other elements in impacting life histories of freshwater zooplankton. Because there is much evidence indicating a pivotal role for iron (Fe) in oogenesis, we hypothesized that dietary Fe content will invoke distinct effects on consumer life history compared to P. We tested this hypothesis in four species of Daphnia, by characterizing the relative impact of P and Fe on life history traits, and also measuring changes in Fe kinetics in response to dietary P and Fe. We found that while P had the largest influence on growth rate, Fe was particularly important in impacting reproductive traits. Radiotracer (Fe55) analyses revealed differences in the acquisition and retention rates of Fe between two species of Daphnia. Finally, we found that P‐ and Fe‐supply driven differences in growth and reproduction had significant effects on population growth. These results indicate that Fe can constrain production of freshwater zooplankton. Understanding the interaction between the supply of P in relation to trace elements should provide a clearer picture on how stoichiometric constraints are realized in lakes.
The DNABII family of proteins is comprised of the only nucleoid associated proteins required for nontypeable Haemophilus influenzae biofilm structure
Authors: Devaraj Aishwarya , Buzzo John , Rocco Christopher J. , Bakaletz Lauren O. , Goodman Steven D. 
Published: December 2017

AbstractBiofilms play a central role in the pathobiology of otitis media (OM), bronchitis, sinusitis, conjunctivitis, and pneumonia caused by nontypeable Haemophilus influenzae (NTHI). Our previous studies show that extracellular DNA (eDNA) and DNABII proteins are essential components of biofilms formed by NTHI. The DNABII protein family includes integration host factor (IHF) and the histone‐like protein HU and plays a central role in NTHI biofilm structural integrity. We demonstrated that immunological targeting of these proteins during NTHI‐induced experimental OM in a chinchilla model caused rapid clearance of biofilms from the middle ear. Given the essential role of DNABII proteins in maintaining the structure of an NTHI biofilm, we investigated whether any of the other nucleoid associated proteins (NAPs) expressed by NTHI might play a similar role, thereby serving as additional target(s) for intervention. We demonstrated that although several NAPs including H‐NS, CbpA, HfQ and Dps are present within the biofilm extracellular matrix, only the DNABII family of proteins is critical for the structural integrity of the biofilms formed by NTHI. We have also demonstrated that IHF and HU are located at distinct regions within the extracellular matrix of NTHI biofilms formed in vitro, indicative of independent functions of these two proteins.
Complete magnetic field dependence of SABRE‐derived polarization
Authors: Kiryutin Alexey S. , Yurkovskaya Alexandra V. , Zimmermann Herbert , Vieth Hans‐Martin , Ivanov Konstantin L. 
Published: December 2017

Signal amplification by reversible exchange (SABRE) is a promising hyperpolarization technique, which makes use of spin‐order transfer from parahydrogen (the H2 molecule in its singlet spin state) to a to‐be‐polarized substrate in a transient organometallic complex, termed the SABRE complex. In this work, we present an experimental method for measuring the magnetic field dependence of the SABRE effect over an ultrawide field range, namely, from 10 nT to 10 T. This approach gives a way to determine the complete magnetic field dependence of SABRE‐derived polarization. Here, we focus on SABRE polarization of spin‐1/2 hetero‐nuclei, such as 13C and 15N and measure their polarization in the entire accessible field range; experimental studies are supported by calculations of polarization. Features of the field dependence of polarization can be attributed to level anticrossings in the spin system of the SABRE complex. Features at magnetic fields of the order of 100 nT–1 μT correspond to “strong coupling” of protons and hetero‐nuclei, whereas features found in the mT field range stem from “strong coupling” of the proton system. Our approach gives a way to measuring and analyzing the complete SABRE field dependence, to probing NMR parameters of SABRE complexes and to optimizing the polarization value.
Prospective motion correction enables highest resolution time‐of‐flight angiography at 7T
Authors: Mattern Hendrik , Sciarra Alessandro , Godenschweger Frank , Stucht Daniel , Lüsebrink Falk , Rose Georg , Speck Oliver 
Published: December 2017

PurposeHigher magnetic field strengths enable time‐of‐flight (TOF) angiography with higher resolution to depict small‐vessel pathologies. However, this potential is limited by the subject's ability to remain motionless. Even small‐scale, involuntary motion can degrade vessel depiction, thus limiting the effective resolution. The aim of this study was to overcome this resolution limit by deploying prospectively motion‐corrected (PMC) TOF.MethodsAn optical, marker‐based, in‐bore tracking system was used to update the imaging volume prospectively according to the subject's head motion. PMC TOF was evaluated in 12 healthy, cooperative subjects at isotropic resolution of up to 150 μm. Image quality was assessed qualitatively through reader rating and quantitatively with the average edge‐strength metric.ResultsPMC significantly increased the average edge strength and qualitatively improved the vessel depiction in nine out of 11 cases. Image quality was never degraded by motion correction. PMC also enabled acquisition of the highest resolution human brain in vivo TOF angiography to date.ConclusionWith PMC enabled, high‐resolution TOF is able to visualize brain vasculature beyond the effective resolution limit. Magn Reson Med 80:248–258, 2018. © 2017 International Society for Magnetic Resonance in Medicine.
Cardiac gating using scattering of an 8‐channel parallel transmit coil at 7T
Authors: Jaeschke Sven H.F. , Robson Matthew D. , Hess Aaron T. 
Published: December 2017

PurposeTo establish a cardiac signal from scattering matrix or scattering coefficient measurements made on a 7T 8‐channel parallel transmit (pTx) system, and to evaluate its use for cardiac gating.MethodsMeasurements of the scattering matrix and scattering coefficients were acquired using a monitoring pulse sequence and during a standard cine acquisition, respectively. Postprocessing used an independent component analysis and gating feature identification. The effect of the phase of the excitation radiofrequency (RF) field (
shim) on the cardiac signal was simulated for multiple
shim configurations, and cine images were reconstructed from both the scattering coefficients and electrocardiogram (ECG).ResultsThe cardiac motion signal was successfully identified in all subjects with a mean signal‐to‐noise ratio of 33.1 and 5.7 using the scattering matrix and scattering coefficient measurements, respectively. The dominant gating feature in the cardiac signal was a peak aligned with end‐systole that occurred on average at 311 and 391 ms after the ECG trigger, with a mean standard deviation of 13.4 and 18.1 ms relative to ECG when using the scattering matrix and scattering coefficients measurements, respectively. The scattering coefficients showed a dependence on
shim with some shim configurations not showing any cardiac signal. Cine images were successfully reconstructed using the scattering coefficients with minimal differences compared to those using ECG.ConclusionWe have shown that the scattering of a pTx RF coil can be used to estimate a cardiac signal, and that scattering matrix and coefficients can be used to cardiac gate MRI acquisitions with the scattering matrix providing a superior cardiac signal. Magn Reson Med 80:633–640, 2018. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.