bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nuclear Protein Sam68 Interacts with the Enterovirus 71 Internal Ribosome Entry Site and Positively Regulates Viral Protein Translation
Authors: Zhang Hua , Song Lei , Cong Haolong , Tien Po 
Published: July 2015

ABSTRACTEnterovirus 71 (EV71) recruits various cellular factors to assist in the replication and translation of its genome. Identification of the host factors involved in the EV71 life cycle not only will enable a better understanding of the infection mechanism but also has the potential to be of use in the development of antiviral therapeutics. In this study, we demonstrated that the cellular factor 68-kDa Src-associated protein in mitosis (Sam68) acts as an internal ribosome entry site (IRES)trans-acting factor (ITAF) that binds specifically to the EV71 5′ untranslated region (5′UTR). Interaction sites in both the viral IRES (stem-loops IV and V) and the heterogeneous nuclear ribonucleoprotein K homology (KH) domain of Sam68 protein were further mapped using an electrophoretic mobility shift assay (EMSA) and biotin RNA pulldown assay. More importantly, dual-luciferase (firefly) reporter analysis suggested that overexpression of Sam68 positively regulated IRES-dependent translation of virus proteins. In contrast, both IRES activity and viral protein translation significantly decreased in Sam68 knockdown cells compared with the negative-control cells treated with short hairpin RNA (shRNA). However, downregulation of Sam68 did not have a significant inhibitory effect on the accumulation of the EV71 genome. Moreover, Sam68 was redistributed from the nucleus to the cytoplasm and interacts with cellular factors, such as poly(rC)-binding protein 2 (PCBP2) and poly(A)-binding protein (PABP), during EV71 infection. The cytoplasmic relocalization of Sam68 in EV71-infected cells may be involved in the enhancement of EV71 IRES-mediated translation. Since Sam68 is known to be a RNA-binding protein, these results provide direct evidence that Sam68 is a novel ITAF that interacts with EV71 IRES and positively regulates viral protein translation.IMPORTANCEThe nuclear protein Sam68 is found as an additional new host factor that interacts with the EV71 IRES during infection and could potentially enhance the translation of virus protein. To our knowledge, this is the first report that describes Sam68 actively participating in the life cycle of EV71 at a molecular level. These studies will not only improve our understanding of the replication of EV71 but also have the potential for aiding in developing a therapeutic strategy against EV71 infection.
Pim Kinase Interacts with Nonstructural 5A Protein and Regulates Hepatitis C Virus Entry
Authors: Park Chorong , Min Saehong , Park Eun-Mee , Lim Yun-Sook , Kang Sangmin , Suzuki Tetsuro , Shin Eui-Cheol , Hwang Soon B. 
Published: July 2015

ABSTRACT

The life cycle of hepatitis C virus (HCV) is highly dependent on host cellular proteins for virus propagation. In order to identify the cellular factors involved in HCV propagation, we performed protein microarray assay using the HCV nonstructural 5A (NS5A) protein as a probe. Of ∼9,000 human cellular proteins immobilized in a microarray, approximately 90 cellular proteins were identified as NS5A interactors. Of these candidates, Pim1, a member of serine/threonine kinase family composed of three different isoforms (Pim1, Pim2, and Pim3), was selected for further study. Pim kinases share a consensus sequence which overlaps with kinase activity. Pim kinase activity has been implicated in tumorigenesis. In the present study, we verified the physical interaction between NS5A and Pim1 by both
in vitro
pulldown and coimmunoprecipitation assays. Pim1 interacted with NS5A through amino acid residues 141 to 180 of Pim1. We demonstrated that protein stability of Pim1 was increased by NS5A protein and this increase was mediated by protein interplay. Small interfering RNA (siRNA)-mediated knockdown or pharmacological inhibition of Pim kinase abrogated HCV propagation. By employing HCV pseudoparticle entry and single-cycle HCV infection assays, we further demonstrated that Pim kinase was involved in HCV entry at a postbinding step. These data suggest that Pim kinase may represent a new host factor for HCV entry.

IMPORTANCE
Pim1 is an oncogenic serine/threonine kinase. HCV NS5A protein physically interacts with Pim1 and contributes to Pim1 protein stability. Since Pim1 protein expression level is upregulated in many cancers, NS5A-mediated protein stability may be associated with HCV pathogenesis. Either gene silencing or chemical inhibition of Pim kinase abrogated HCV propagation in HCV-infected cells. We further showed that Pim kinase was specifically required at an early entry step of the HCV life cycle. Thus, we have identified Pim kinase not only as an HCV cell entry factor but also as a new anti-HCV therapeutic target.
Non-invasive prenatal diagnosis using fetal DNA in maternal plasma: a preliminary study for identification of paternally-inherited alleles using single nucleotide polymorphisms
Authors: Chen J J , Tan J A M A , Chua K H , Tan P C , George E 
Published: July 2015

ObjectivesSingle nucleotide polymorphism (SNP) with a mutation can be used to identify the presence of the paternally-inherited wild-type or mutant allele as result of the inheritance of either allele in the fetus and allows the prediction of the fetal genotype. This study aims to identify paternal SNPs located at the flanking regions upstream or downstream from the β-globin gene mutations at CD41/42 (HBB:c.127_130delCTTT), IVS1-5 (HBB:c.92+5G>C) and IVS2-654 (HBB:c.316-197C>T) using free-circulating fetal DNA.SettingHaematology Lab, Department of Biomedical Science, University of Malaya.ParticipantsEight couples characterised as β-thalassaemia carriers where both partners posed the same β-globin gene mutations at CD41/42, IVS1-5 and IVS2-654, were recruited in this study.Outcome measuresGenotyping was performed by allele specific-PCR and the locations of SNPs were identified after sequencing alignment.ResultsGenotype analysis revealed that at least one paternal SNP was present for each of the couples. Amplification on free-circulating DNA revealed that the paternal mutant allele of SNP was present in three fcDNA. Thus, the fetuses may be β-thalassaemia carriers or β-thalassaemia major. Paternal wild-type alleles of SNP were present in the remaining five fcDNA samples, thus indicating that the fetal genotypes would not be homozygous mutants.ConclusionsThis preliminary research demonstrates that paternal allele of SNP can be used as a non-invasive prenatal diagnosis approach for at-risk couples to determine the β-thalassaemia status of the fetus.
Providers contextualise care more often when they discover patient context by asking: meta-analysis of three primary data sets
Authors: Schwartz Alan , Weiner Saul J , Binns-Calvey Amy , Weaver Frances M 
Published: July 2015

ObjectivesOne important component of patient-centred care is provider incorporation of patient contextual factors—life circumstances relevant to their care—in managing the patient's health. The current study uses data sets collected from direct observation of care to examine ifhowa provider learns contextual information influences whether the provider incorporates the information into a care plan.MethodsThree data sets were reanalysed: a research study with physicians, a quality improvement project with physicians and a performance measurement project with telephone health assistants. In each data set, investigators compute rates of incorporation of patient contextual factors into the care plan for encounters in which factors were elicited in response to a probe by the provider versus revealed spontaneously by the patient. We report the rates, CIs and associated ORs for each study and overall using a random effects meta-analysis.ResultsProviders elicited 57%, 49% and 30% of patient contextual factors identified in encounters in each data set. Patient contextual factors identified in response to probes were incorporated into the plan of care more frequently than those revealed spontaneously by patients (68% vs 46%, 71% vs 54% and 93% vs 77%, respectively). The summary OR for incorporation of patient contextual factors into the care plan when the factor was probed versus revealed spontaneously was 4.16 (95% CI 2.0 to 8.6). While this estimate was associated with significant heterogeneity (I2=76%), the ORs for the individual data sets were 2.53 (1.4 to 4.5), 6.25 (4.9 to 8.0) and 4.2 (0.9 to 19.3).ConclusionsIn encounters where addressing patient contextual factors may play an important role in care decisions, factors that are elicited actively by the provider are more likely to be incorporated in the care plan than factors revealed spontaneously by the patient. These differences in the care process associated with provider performance can only be demonstrated through direct observation.
Extraneural hemangioblastoma of the kidney: the challenge for clinicopathological diagnosis
Authors: Wu Yong , Wang Tao , Zhang Pei-Pei , Yang Xiaoqun , Wang Jian , Wang Chao-Fu 
Published: July 2015

BackgroundHemangioblastoma is a benign cerebellar tumour which may occur as a sporadic entity or in association with von Hippel-Lindau (VHL) disease in approximately 25% of cases. Renal hemangioblastoma (RH) is an extremely rare and newly recognised tumour. Here, we describe five cases of RH, one discovered by CT in an accident and the other four detected during routine examinations.MethodsFive cases of renal hemangioblastoma retrieved from the Department of Pathology, Fudan University Shanghai Cancer Center were studied and the literatures were reviewed. Immunohistochemistry was used to differentiate and confirm this tumour.ResultsPathological examination following tumour resection revealed RH in all cases, the first patient was also diagnosed with renal cell carcinoma (RCC), suggesting the possibility of VHL syndrome, but PCR sequencing analysis of the VHL gene confirmed no mutation in any of the three exons, implying sporadic disease .Histologically, the tumours were circumscribed, composed of sheets of oval or polygonal cells and a prominent vascular network. Tumour cells had pleomorphic nuclei, but mitotic figures were rare. The diagnosis of hemangioblastoma was confirmed by immunohistochemistry.ConclusionsRH is very rare and is challenging to differentially diagnose. Distinguishing RCC and RH is difficult and each has a different prognosis, so differentiating between them is essential for avoiding over-diagnosis and unnecessary treatment.
Palaeomagnetism of Mesozoic magmatic bodies of the Fuegian Cordillera: implications for the formation of the Patagonian Orocline
Authors: Rapalini Augusto E. , Peroni Javier , Luppo Tomás , Tassone Alejandro , Elena Cerredo María , Esteban Federico , Lippai Horacio , Franciscovilas Juan 
Published: July 2015

Abstract

It is not known whether the Patagonian Orocline, the major bend of the southern Andes at the southern tip of South America, is a primary or secondary feature. Palaeomagnetic data along the Patagonian Orocline are still too scarce to provide a reliable and unambiguous answer to this question. New palaeomagnetic results on Late Jurassic–Late Cretaceous magmatic units along the central segment of the Fuegian Cordillera are reported. Data from four Late Cretaceous small intrusions and three sites on Late Jurassic–Early Cretaceous metabasalts and metagabbros showed anticlockwise declination deviations between 21° and 46° with respect to South America. From these and previous data, a picture of a nearly homogeneous post-Late Cretaceous regional rotation of the central Fuegian Cordillera is suggested. This supports a model of nearly 30° of anticlockwise secondary bending of the Patagonian Orocline since the Late Cretaceous (72 Ma). Lack of rotation of post-50 Ma sedimentary rocks exposed to the north of our study region, and larger rotations (of
c.
90°) reported to the south of it suggest that a geographical and/or temporal progression of rotation values from south to north in the Fuegian part of the Patagonian Orocline should be investigated.
Determining the timing of formation of the Rawil Depression in the Helvetic Alps by palaeomagnetic and structural methods
Authors: Cardello G. L. , Almqvist B. S. G. , Hirt A. M. , Mancktelow N. S. 
Published: July 2015

Abstract
Anisotropy of magnetic susceptibility, palaeomagnetism and structural methods are used in order to test the relative timing of antiform updoming and formation of the Rawil Depression in the Helvetic Alps. Samples were collected from all nappes currently exposed in the study region. The magnetic fabric is consistent with extension oblique and parallel to the regional fold trend and with palaeostress reconstructions from fault planes and veins. Palaeomagnetic analyses show a stable characteristic remanence (ChRM), with samples recording both normal and reverse polarity. A successful fold test performed across the antiformal dome structure suggests that the palaeomagnetic signal was acquired prior to doming. By comparison with thermochronometric data, the ChRM was acquired between 25 and 10 Ma and is pre- to synfolding. A secondary post-doming palaeomagnetic component (A), whose magnetization is likely to have occurred between 10 and 3.5 Ma, appears to be too steep with regards to the inclination of the Earth's field, suggesting recent large-scale tilting has occurred in the region. These combined analyses indicate that widespread orogen-parallel extension occurred prior to the formation of the Rawil Depression, which is finally interpreted as the result of a stepover structure at the curvature between Central and Western Alps.
Cellular Mechanisms Underlying Complete Hematological Response of Chronic Myeloid Leukemia to BRAF and MEK1/2 Inhibition in a Patient with Concomitant Metastatic Melanoma
Authors: Andrews Miles C. , Turner Natalie , Boyd Janis , Roberts Andrew W. , Grigg Andrew P. , Behren Andreas , Cebon Jonathan 
Published: July 2015

Abstract
Purpose: Targeted MEK inhibition is an emerging therapy in a number of solid tumors. It holds particular promise in BRAF V600E mutation–positive malignant melanoma, where constitutive activation and cell growth through the MAP kinase (MAPK) pathway is well established. In vitro and preclinical research indicates that MAPK pathway activation is important in chronic myeloid leukemia (CML) leukemogenesis; however, the potential of MEK inhibition has not yet been investigated clinically in the setting of such hematologic malignancies.
Experimental Design: We report a case of complete hematologic response of CML to MEK inhibition in a patient with synchronous metastatic melanoma, who received treatment with combination BRAF and MEK1/2 inhibitors. We studied the effects of these agents on proliferation and outgrowth of myeloid precursors, and longitudinal shifts in peripheral blood phenotyping during the course of treatment. A model cell line system was used to examine the effects of dabrafenib and trametinib on MAPK and BCR–ABL1 signaling.
Results: After 35 weeks on treatment with BRAF and MEK inhibitors, complete hematologic response was observed without recourse to BCR–ABL1–targeted therapy. MEK inhibition was principally responsible for impaired proliferation of both mature and primitive myeloid precursors, as well as growth and hemoglobinization of erythroid precursors. Paradoxical activation of the MAPK pathway was seen in response to BRAF inhibitor therapy but this was easily overcome by clinically relevant doses of concurrent MEK inhibitor.
Conclusions: These studies suggest that further evaluation of the optimal MAPK targeting approach is warranted to extend therapeutic options in CML. Clin Cancer Res; 21(23); 5222–34. ©2015 AACR.
Perception and Production of Singleton and Geminate Stops in Japanese: Implications for the Theory of Acoustic Invariance
Authors: Amano Shigeaki , Hirata Y. 
Published: July 2015

AbstractThe theory of relational acoustic invariance claims that there are stable acoustic properties in speech signals that correspond to a phonological feature, and that the perception system utilizes these acoustic properties for stable perception of a phoneme. The present study examines whether such an invariance exists in native listeners' perception of Japanese singleton and geminate stops despite variability in speaking rate and word length, and whether this perception corresponds to production. Native Japanese listeners identified singleton and geminate stops in continua of 3- and 4-mora words spoken at different speaking rates. Results indicated that the perception boundary is well predicted by a linear function with two variables: durations of stop closure and the (C)V(C)CV portion (with the contrasting stops underlined) of the 3- and 4-mora words. In addition, these two variables were in a consistent relationship for both perception and production of words containing 2-4 moras. The results support the relational acoustic invariance theory.
Point-of-care testing and INR within-subject variation in patients receiving a constant dose of vitamin K antagonist
Authors: Biedermann Joseph S. , Kruip Marieke J. H. A. , van den Besselaar A. M. H. P. 
Published: July 2015

SummaryMany patients treated with vitamin K antagonists (VKA) determine their INR using point-of-care (POC) whole blood coagulation monitors. The primary aim of the present study was to assess the INR within-subject variation in self-testing patients receiving a constant dose of VKA. The second aim of the study was to derive INR imprecision goals for whole blood coagulation monitors. Analytical performance goals for INR measurement can be derived from the average biological within-subject variation. Fifty-six Thrombosis Centres in the Netherlands were invited to select self-testing patients who were receiving a constant dose of either acenocoumarol or phenprocoumon for at least six consecutive INR measurements. In each patient, the coefficient of variation (CV) of INRs was calculated. One Thrombosis Centre selected regular patients being monitored with a POC device by professional staff. Sixteen Dutch Thrombosis Centres provided results for 322 selected patients, all using the CoaguChek XS. The median within-subject CV in patients receiving acenocoumarol (10.2 %) was significantly higher than the median CV in patients receiving phenprocoumon (8.6 %) (p = 0.001). The median CV in low-target intensity acenocoumarol self-testing patients (10.4 %) was similar to the median CV in regular patients monitored by professional staff (10.2 %). Desirable INR analytical imprecision goals for POC monitoring with CoaguChek XS in patients receiving either low-target intensity acenocoumarol or phenprocoumon were 5.1 % and 4.3 %, respectively. The approximate average value for the imprecision of the CoaguChek XS, i. e. 4 %, is in agreement with these goals.
Sirt7 Contributes to Myocardial Tissue Repair by Maintaining Transforming Growth Factor-β Signaling Pathway
Authors: Araki Satoshi , Izumiya Yasuhiro , Rokutanda Taku , Ianni Alessandro , Hanatani Shinsuke , Kimura Yuichi , Onoue Yoshiro , Senokuchi Takafumi , Yoshizawa Tatsuya , Yasuda Osamu , Koitabashi Norimichi , Kurabayashi Masahiko , Braun Thomas , Bober Eva , Yamagata Kazuya , Ogawa Hisao 
Published: July 2015

Background—
Sirt7, 1 of the 7 members of the mammalian sirtuin family, promotes oncogenic transformation. Tumor growth and metastasis require fibrotic and angiogenic responses. Here, we investigated the role of Sirt7 in cardiovascular tissue repair process.

Methods and Results—

In wild-type mice, Sirt7 expression increased in response to acute cardiovascular injury, including myocardial infarction and hind-limb ischemia, particularly at the active wound healing site. Compared with wild-type mice, homozygous Sirt7-deficient (Sirt7
−/−
) mice showed susceptibility to cardiac rupture after myocardial infarction, delayed blood flow recovery after hind-limb ischemia, and impaired wound healing after skin injury. Histological analysis showed reduced fibrosis, fibroblast differentiation, and inflammatory cell infiltration in the border zone of infarction in Sirt7
−/−
mice. In vitro, Sirt7
−/−
mouse–derived or Sirt7 siRNA–treated cardiac fibroblasts showed reduced transforming growth factor-β signal activation and low expression levels of fibrosis-related genes compared with wild-type mice–derived or control siRNA–treated cells. These changes were accompanied by reduction in transforming growth factor receptor I protein. Loss of Sirt7 activated autophagy in cardiac fibroblasts. Transforming growth factor-β receptor I downregulation induced by loss of Sirt7 was blocked by autophagy inhibitor, and interaction of Sirt7 with protein interacting with protein kinase-Cα was involved in this process.

Conclusion—
Sirt7 maintains transforming growth factor receptor I by modulating autophagy and is involved in the tissue repair process.
Genesis 1-3: Augustine and Origen on the coats of skins
Authors: Pârvan Alexandra 
Published: July 2015

Abstract
This paper explores Origen’s and Augustine’s interpretations of Gen. 3,21, which regards the coats of skins that God gave to Adam and Eve after they had sinned. I propose the notion of man’s “state of intermediateness” as a basis for examining both authors’ understanding of the skin tunics, and for revealing the similarities and distinctive dissimilarities in their interpretations. I also investigate how Origen’s and Augustine’s different readings of the two accounts of man’s creation, in Gen. 1,27 and Gen. 2,7, can be connected with their understanding of Gen. 3,21. I conclude by showing how despite some striking similarities that link Augustine’s interpretation of the skin coats to Origen’s view, and even despite the fact that Augustine reiterates an already-established symbolism, his exegesis of the skin tunics still bears a particular relevance and originality.
Prace Komisji Środkowoeuropejskiej Prezentacja cyklu
Authors: Taczyńska Katarzyna 
Published: July 2015

Presentation of the book series "Prace Komisji Środkowoeuropejskiej" Presentation of the book series "Prace Komisji Środkowoeuropejskiej" (Works of the Central Europe Commitee), edited and published by the PAU (Polish Academy of Arts and Sciences) in Cracow.