bluuebunny/crossref_metadata_2025_split huggingface dataset:
The WTO in an Era of Preferential Trade Agreements: Thick and Thin Institutions in Global Trade Governance
Authors: TROMMER SILKE 
Published: February 2017

AbstractThis article examines how fragmentation of the global trade regime into preferential agreements, built on a multilateral baseline of World Trade Organization (WTO) rules, affects trade governance. The analysis relies on 105 interviews with trade policy professionals in core WTO members and a conceptual distinction between ‘thick’ and ‘thin’ institutionalism to capture institutional changes in the global trade governance architecture. The WTO's thick institutionalism facilitates institutionalized interactions among members of the trade policy community that are essential for transparency and dialogue and the rule of law character of the trade regime. It secures the continued belief of trade policy professionals in the WTO's centrality in trade governance. The thin institutionalism of the network of preferential agreements spells the return toà la carteforms of trade governance and benefits those with the technical and political capacity to successfully navigate the fragmented governance architecture. Ongoing institutional transformations shift global trade governance away from rules-based back to more power-based forms.
The state of American health care: November 2016 to November 2020, a look forward
Authors: Marmor Theodore , Gusmano Michael K. 
Published: February 2017

AbstractThe election of Donald Trump, coupled with the retention of Republican majorities in the US House of Representatives and Senate, raises questions about future of the Patient Protection and Affordable Care Act, the structure and funding of the country’s public health insurance programs – Medicare, Medicaid and the Child Health Insurance Program – and the direction of health policy in the United States, more generally. Political scientists are not renowned for their capacity to predict the future and many of those who forecast election results have received criticism in recent weeks for failing to predict the Trump victory. While the future is uncertain, it is possible for social scientists to offer a ‘conditional causal analysis’ about the future. This essay is an effort to think about the likely shape of American health care between now and the next US presidential election.
Mesenchymal stromal cells inhibit CD25 expression via the mTOR pathway to potentiate T-cell suppression
Authors: Yoo Hyun Seung , Lee Kyuheon , Na Kwangmin , Zhang Yong Xu , Lim Hyun-Ja , Yi TacGhee , Song Sun U , Jeon Myung-Shin 
Published: February 2017

AbstractMesenchymal stromal cells (MSCs) are known to suppress T-cell activation and proliferation. Several studies have reported that MSCs suppress CD25 expression in T cells. However, the molecular mechanism underlying MSC-mediated suppression of CD25 expression has not been fully examined. Here, we investigated the mTOR pathway, which is involved in CD25 expression in T cells. We showed that MSCs inhibited CD25 expression, which was restored in the presence of an inducible nitric oxide synthase (iNOS) inhibitor. Since CD25 mRNA expression was not inhibited, we focused on determining whether MSCs modulated components of the mTOR pathway in T cells. MSCs increased the phosphorylation of liver kinase B1 (LKB1) and AMP-activated protein kinase (AMPK) and decreased the phosphorylation of ribosomal protein S6 kinase 1 (S6K1) and eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1). In addition, the expression of 4E-BP1 increased dramatically in the presence of MSCs. An m7GTP pull-down assay showed increased binding of 4E-BP1 to the 5′ cap-binding eukaryotic translation initiation factor 4E (eIF4E) complex in the presence of MSCs, which resulted in inhibition of mRNA translation. Treatment with 4EGI-1, a synthetic inhibitor of mRNA translation, also reduced CD25 expression in T cells. Polysome analysis confirmed decreased CD25 mRNA in the polysome-rich fraction in the presence of MSCs. Taken together, our results showed that nitric oxide, produced by MSCs, inhibits CD25 translation through regulation of the LKB1-AMPK-mTOR pathway to suppress T cells.
CARMA2sh and ULK2 control pathogen-associated molecular patterns recognition in human keratinocytes: psoriasis-linked CARMA2sh mutants escape ULK2 censorship
Authors: Scudiero Ivan , Mazzone Pellegrino , D'Andrea Luca E , Ferravante Angela , Zotti Tiziana , Telesio Gianluca , De Rubis Gabriele , Reale Carla , Pizzulo Maddalena , Muralitharan Shanmugakonar , Vito Pasquale , Stilo Romania 
Published: February 2017

AbstractThe molecular complexes formed by specific members of the family of CARMA proteins, the CARD domain-containing adapter molecule BCL10 and MALT1 (CBM complex) represent a central hub in regulating activation of the pleiotropic transcription factor NF-κB. Recently, missense mutations in CARMA2sh have been shown to cause psoriasis in a dominant manner and with high penetrancy. Here, we demonstrate that in human keratinocytes CARMA2sh plays an essential role in the signal transduction pathway that connects pathogen-associated molecular patterns recognition to NF-κB activation. We also find that the serine/threonine kinase ULK2 binds to and phosphorylates CARMA2sh, thereby inhibiting its capacity to activate NF-κB by promoting lysosomal degradation of BCL10, which is essential for CARMA2sh-mediated NF-κB signaling. Remarkably, CARMA2sh mutants associated with psoriasis escape ULK2 inhibition. Finally, we show that a peptide blocking CARD-mediated BCL10 interactions reduces the capacity of psoriasis-linked CARMA2sh mutants to activate NF-κB. Our work elucidates a fundamental signaling mechanism operating in human keratinocytes and opens to novel potential tools for the therapeutical treatment of human skin disorders.
Differential regulation of the Epr3 receptor coordinates membrane-restricted rhizobial colonization of root nodule primordia
Authors: Kawaharada Yasuyuki , Nielsen Mette W. , Kelly Simon , James Euan K. , Andersen Kasper R. , Rasmussen Sheena R. , Füchtbauer Winnie , Madsen Lene H. , Heckmann Anne B. , Radutoiu Simona , Stougaard Jens 
Published: February 2017

AbstractIn Lotus japonicus, a LysM receptor kinase, EPR3, distinguishes compatible and incompatible rhizobial exopolysaccharides at the epidermis. However, the role of this recognition system in bacterial colonization of the root interior is unknown. Here we show that EPR3 advances the intracellular infection mechanism that mediates infection thread invasion of the root cortex and nodule primordia. At the cellular level, Epr3 expression delineates progression of infection threads into nodule primordia and cortical infection thread formation is impaired in epr3 mutants. Genetic dissection of this developmental coordination showed that Epr3 is integrated into the symbiosis signal transduction pathways. Further analysis showed differential expression of Epr3 in the epidermis and cortical primordia and identified key transcription factors controlling this tissue specificity. These results suggest that exopolysaccharide recognition is reiterated during the progressing infection and that EPR3 perception of compatible exopolysaccharide promotes an intracellular cortical infection mechanism maintaining bacteria enclosed in plant membranes.
Synergistic effects of dimethyloxallyl glycine and recombinant human bone morphogenetic protein-2 on repair of critical-sized bone defects in rats
Authors: Qi Xin , Liu Yang , Ding Zhen-yu , Cao Jia-qing , Huang Jing-huan , Zhang Jie-yuan , Jia Wei-tao , Wang Jing , Liu Chang-sheng , Li Xiao-lin 
Published: February 2017

AbstractIn bone remodeling, osteogenesis is closely coupled to angiogenesis. Bone tissue engineering using multifunctional bioactive materials is a promising technique which has the ability to simultaneously stimulate osteogenesis and angiogenesis for repair of bone defects. We developed mesoporous bioactive glass (MBG)-doped poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) composite scaffolds as delivery vehicle. Two bioactive molecules, dimethyloxalylglycine (DMOG), a small-molecule angiogenic drug, and recombinant human bone morphogenetic protein-2 (rhBMP-2), an osteoinductive growth factor, were co-incorporated into the scaffold. The synergistic effects of DMOG and rhBMP-2 released in the composite scaffolds on osteogenic and angiogenic differentiation of hBMSCs were investigated using real-time quantitative polymerase chain reaction and western blotting. Moreover, in vivo studies were conducted to observe bone regeneration and vascular formation of critical-sized bone defects in rats using micro-computed tomography, histological analyses, Microfil® perfusion, fluorescence labeling, and immunohistochemical analysis. The results showed that DMOG and rhBMP-2 released in the MBG-PHBHHx scaffolds did exert synergistic effects on the osteogenic and angiogenic differentiation of hBMSCs. Moreover, DMOG and rhBMP-2 produced significant increases in newly-formed bone and neovascularization of calvarial bone defects in rats. It is concluded that the co-delivery strategy of both rhBMP-2 and DMOG can significantly improve the critical-sized bone regeneration.
Ricin uses arginine 235 as an anchor residue to bind to P-proteins of the ribosomal stalk
Authors: Zhou Yijun , Li Xiao-Ping , Chen Brian Y. , Tumer Nilgun E. 
Published: February 2017

AbstractRicin toxin A chain (RTA) binds to stalk P-proteins to reach the α–sarcin/ricin loop (SRL) where it cleaves a conserved adenine. Arginine residues at the RTA/RTB interface are involved in this interaction. To investigate the individual contribution of each arginine, we generated single, double and triple arginine mutations in RTA. The R235A mutation reduced toxicity and depurination activity more than any other single arginine mutation in yeast. Further reduction in toxicity, depurination activity and ribosome binding was observed when R235A was combined with a mutation in a nearby arginine. RTA interacts with the ribosome via a two-step process, which involves slow and fast interactions. Single arginine mutations eliminated the fast interactions with the ribosome, indicating that they increase the binding rate of RTA. Arginine residues form a positively charged patch to bind to negatively charged residues at the C-termini of P-proteins. When electrostatic interactions conferred by the arginines are lost, hydrophobic interactions are also abolished, suggesting that the hydrophobic interactions alone are insufficient to allow binding. We propose that Arg235 serves as an anchor residue and cooperates with nearby arginines and the hydrophobic interactions to provide the binding specificity and strength in ribosome targeting of RTA.
Oxygen impairs oligodendroglial development via oxidative stress and reduced expression of HIF-1α
Authors: Brill Christina , Scheuer Till , Bührer Christoph , Endesfelder Stefanie , Schmitz Thomas 
Published: February 2017

AbstractThe premature increase of oxygen tension may contribute to oligodendroglial precursor cell (OPC) damage in preterm infants. Fetal OPCs are exposed to low oxygen tissue tensions not matched when cells are cultured in room air. Maturation (A2B5, O4, O1, MBP, CNP, arborization), oxidative stress (nitrotyrosine Western blot, NRF2 and SOD2 expression), apoptosis (TUNEL), proliferation (Ki67), and expression of transcription factors regulated by Hypoxia-Inducible-Factor-1-alpha (Hif-1α) expressed in OPCs (Olig1, Olig2, Sox9, Sox10) were assessed in rat OPCs and OLN93 cells cultured at 5% O2 and 21% O2. Influences of Hif-1α were investigated by Hif-1α luciferase reporter assays and Hif-1α-knockdown experiments. At 21% O2, cell proliferation was decreased and process arborization of OPCs was reduced. Expression of MBP, CNP, Olig1, Sox9 and Sox10 was lower at 21% O2, while Nrf2, SOD2, nitrotyrosine were increased. Apoptosis was unchanged. Luciferease reporter assay in OLN93 cells indicated increased Hif-1α activity at 5% O2. In OLN93 cells at 5% O2, Hif-1α knockdown decreased the expression of MBP and CNP, similar to that observed at 21% O2. These data indicate that culturing OPCs at 21% O2 negatively affects development and maturation. Both enhanced oxidative stress and reduced expression of Hif-1α-regulated genes contribute to these hyperoxia-induced changes.
Evaluating Variant Calling Tools for Non-Matched Next-Generation Sequencing Data
Authors: Sandmann Sarah , de Graaf Aniek O. , Karimi Mohsen , van der Reijden Bert A. , Hellström-Lindberg Eva , Jansen Joop H. , Dugas Martin 
Published: February 2017

AbstractValid variant calling results are crucial for the use of next-generation sequencing in clinical routine. However, there are numerous variant calling tools that usually differ in algorithms, filtering strategies, recommendations and thus, also in the output. We evaluated eight open-source tools regarding their ability to call single nucleotide variants and short indels with allelic frequencies as low as 1% in non-matched next-generation sequencing data: GATK HaplotypeCaller, Platypus, VarScan, LoFreq, FreeBayes, SNVer, SAMtools and VarDict. We analysed two real datasets from patients with myelodysplastic syndrome, covering 54 Illumina HiSeq samples and 111 Illumina NextSeq samples. Mutations were validated by re-sequencing on the same platform, on a different platform and expert based review. In addition we considered two simulated datasets with varying coverage and error profiles, covering 50 samples each. In all cases an identical target region consisting of 19 genes (42,322 bp) was analysed. Altogether, no tool succeeded in calling all mutations. High sensitivity was always accompanied by low precision. Influence of varying coverages- and background noise on variant calling was generally low. Taking everything into account, VarDict performed best. However, our results indicate that there is a need to improve reproducibility of the results in the context of multithreading.
Evidence for risk extrapolation in decision making by tadpoles
Authors: Crane Adam L. , Ferrari Maud C. O. 
Published: February 2017

AbstractThrough time, the activity patterns, morphology, and development of both predators and prey change, which in turn alter the relative vulnerability of prey to their coexisting predators. Recognizing these changes can thus allow prey to make optimal decisions by projecting risk trends into the future. We used tadpoles (Lithobates sylvaticus) to test the hypothesis that tadpoles can extrapolate information about predation risk from past information. We exposed tadpoles to an odour that represented either a temporally consistent risk or an increasing risk. When tested for their response to the odour, the initial antipredator behaviour of tadpoles did not differ, appearing to approach the limit of their maximum response, but exposure to increasing risk induced longer retention of these responses. When repeating the experiment using lower risk levels, heightened responses occurred for tadpoles exposed to increasing risk, and the strongest responses were exhibited by those that received an abrupt increase compared to a steady increase. Our results indicate that tadpoles can assess risk trends through time and adjust their antipredator responses in a way consistent with an extrapolated trend. This is a sophisticated method for prey to avoid threats that are becoming more (or less) dangerous over part of their lifespan.
Silencing salusin-β attenuates cardiovascular remodeling and hypertension in spontaneously hypertensive rats
Authors: Ren Xing-Sheng , Ling Li , Zhou Bing , Han Ying , Zhou Ye-Bo , Chen Qi , Li Yue-Hua , Kang Yu-Ming , Zhu Guo-Qing 
Published: February 2017

AbstractSalusin-β is a bioactive peptide involved in vascular smooth muscle cell proliferation, vascular fibrosis and hypertension. The present study was designed to determine the effects of silencing salusin-β on hypertension and cardiovascular remodeling in spontaneously hypertensive rats (SHR). Thirteen-week-old male SHR and normotensive Wistar-Kyoto rats (WKY) were subjected to intravenous injection of PBS, adenoviral vectors encoding salusin-β shRNA (Ad-Sal-shRNA) or a scramble shRNA. Salusin-β levels in plasma, myocardium and mesenteric artery were increased in SHR. Silencing salusin-β had no significant effect on blood pressure in WKY, but reduced blood pressure in SHR. It reduced the ratio of left ventricle weight to body weight, cross-sectional areas of cardiocytes and perivascular fibrosis, and decreased the media thickness and the media/lumen ratio of arteries in SHR. Silencing salusin-β almost normalized plasma norepinephrine and angiotensin II levels in SHR. It prevented the upregulation of angiotensin II and AT1 receptors, and reduced the NAD(P)H oxidase activity and superoxide anion levels in myocardium and mesenteric artery of SHR. Knockdown of salusin-β attenuated cell proliferation and fibrosis in vascular smooth muscle cells from SHR. These results indicate that silencing salusin-β attenuates hypertension and cardiovascular remodeling in SHR.
Regulation of photosensitisation processes by an RNA aptamer
Authors: Thoa Tran Thi Thanh , Minagawa Noriko , Aigaki Toshiro , Ito Yoshihiro , Uzawa Takanori 
Published: February 2017

AbstractOne of the most powerful attributes of proteins is their ability to bind to and modulate the chemistry of cofactors and prosthetic groups. Here, we demonstrated the ability of an artificial nucleic acid (an aptamer) to similarly control the functionality of a non-biological element. Specifically, we selected an RNA aptamer that binds tris(bipyridine) ruthenium (II), Ru(bpy)32+, an inorganic complex that has attracted intense interest due to its photoredox chemistry, including its ability to split water by visible light. We found that a newly discovered aptamer strongly and enantioselectively binds Λ-Ru(bpy)32+ (Kd = 65 nM) and, in doing so, selectively suppresses deactivation via energy transfer, thereby elongating the lifetime of its photo-excited state by four-fold. The ability of the aptamer to enhance this important aspect of Ru(bpy)32+ chemistry illustrates a broader point concerning the potential power of combining in vitro-created biomolecules with non-biological reactants to perform enhanced chemical reactions.
An endoparasitoid wasp influences host DNA methylation
Authors: Kumar Sunil , Kim Yonggyun 
Published: February 2017

AbstractParasitism by endoparasitoid wasps changes the expression of various host genes, and alters host immune and developmental processes. However, it is not clearly understood how parasitism changes host gene expression in a whole genome scale. This study focused on an epigenetic control of Cotesia plutellae, an endoparasitoid wasp, against its host, Plutella xylostella. Two DNA methyltransferases (DNMT-1 and DNMT-2) are encoded in the genome of P. xylostella. In addition, methyl-binding domain proteins (MBDs) and DNA demethylation factor, ten-eleven translation protein (TET) are encoded. DNA methylation of P. xylostella genomic DNA was confirmed by restriction digestion with Gla I specific to 5-methylcytosine. DNA methylation intensity in parasitized (P) larvae was decreased compared to that in nonparasitized (NP) larvae, especially at late parasitic stage, at which expression levels of both DNMT-1 and DNMT-2 were also decreased. DNA demethylation of P. xylostella was confirmed in both NP and P larvae by restriction digestion with PvuRts1I recognizing 5-hydroxymethyl cytosine. Parasitism also suppressed expression levels of TET and MBDs. Treatment of 5-aza-2′-deoxycytidine (AZA) reduced DNA methylation intensity of NP larvae, causing suppression of hemocyte-spreading behavior and delay of immature development. RNA interference of DNMT-1 or DNMT-2 mimicked the adverse effects of AZA.
Relapsing-remitting multiple sclerosis patients display an altered lipoprotein profile with dysfunctional HDL
Authors: Jorissen Winde , Wouters Elien , Bogie Jeroen F. , Vanmierlo Tim , Noben Jean-Paul , Sviridov Denis , Hellings Niels , Somers Veerle , Valcke Roland , Vanwijmeersch Bart , Stinissen Piet , Mulder Monique T. , Remaley Alan T. , Hendriks Jerome J. A. 
Published: February 2017

AbstractLipoproteins modulate innate and adaptive immune responses. In the chronic inflammatory disease multiple sclerosis (MS), reports on lipoprotein level alterations are inconsistent and it is unclear whether lipoprotein function is affected. Using nuclear magnetic resonance (NMR) spectroscopy, we analysed the lipoprotein profile of relapsing-remitting (RR) MS patients, progressive MS patients and healthy controls (HC). We observed smaller LDL in RRMS patients compared to healthy controls and to progressive MS patients. Furthermore, low-BMI (BMI ≤ 23 kg/m2) RRMS patients show increased levels of small HDL (sHDL), accompanied by larger, triglyceride (TG)-rich VLDL, and a higher lipoprotein insulin resistance (LP-IR) index. These alterations coincide with a reduced serum capacity to accept cholesterol via ATP-binding cassette (ABC) transporter G1, an impaired ability of HDL3to suppress inflammatory activity of human monocytes, and modifications of HDL3’s main protein component ApoA-I. In summary, lipoprotein levels and function are altered in RRMS patients, especially in low-BMI patients, which may contribute to disease progression in these patients.
Possibilités et limites du traitement de la dysharmonie dents-arcades par chirurgie maxillo-faciale
Authors: Paulus Christian 
Published: February 2017

Introduction : La dysharmonie dents-arcades autrefois appelée « dysharmonie dento-maxillaire » ou « macrodontie/microdontie relative » correspond à une disproportion de volume entre les dents et les bases osseuses. En présence d’un volume dentaire trop important par rapport à la longueur d’arcade, un traitement avec extraction peut être proposé. Les techniques de « distraction osseuse » mises au point par Ilizarov dans les années 1950 permettent actuellement d’augmenter la longueur d’arcade au maxillaire et à la mandibule. Matériels et méthodes : Les auteurs décriront la mise en œuvre orthodontico-chirurgicale de cette augmentation de longueur d’arcade depuis l’établissement du plan thérapeutique jusqu’à l’obtention d’une longueur d’arcade suffisante ainsi que l’intérêt thérapeutique devant l’encombrement dentaire, la vestibuloversion et les troubles des fonctions orofaciales. Discussion : La distraction est un moyen thérapeutique intéressant à envisager dans la prise en charge de la dysharmonie dents-arcades, qui permet de gagner la longueur d’arcade nécessaire à l’objectif thérapeutique fixé.
Observational Case Series Evaluation of the Granisetron Transdermal Patch System (Sancuso) for the Management of Nausea/Vomiting of Pregnancy
Authors: Le Tran , Adler Michael , Ouillette Holly , Berens Pamela , Smith Judith 
Published: February 2017

Objective The objective of this study was to observe the efficacy of antiemetic therapy (no emesis/retching episodes and no rescue medication use) when granisetron is administered via a transdermal patch system (TDS) in women who are 6 to 14 weeks pregnant when compared with oral ondansetron by evaluating the frequency of the use of rescue medications for control of nausea/vomiting of pregnancy (NVP).
Methods This was an observational case series study to observe the potential benefits of granisetron TDS compared with oral ondansetron for management of NVP in pregnant patients during the first trimester. Dates of data collection were September 1, 2014, through December 31, 2015. There was no direct contact with patient. The oral ondansetron and granisetron TDS patients were matched by age, 4:1. The proportion of patients who received rescue antiemetics was calculated from those patients who continued to experience NVP. Risk factors for NVP were identified and compared between groups. Descriptive statistics were used to describe study results.
Results Patients were prescribed rescue antiemetics in 0/3 patients in the granisetron TDS group compared with 2/12 patients in the oral ondansetron group.
Conclusion Prospective efficacy studies on the use of granisetron TDS for management of NVP are needed to confirm this clinical observation.