bluuebunny/crossref_metadata_2025_split huggingface dataset:
Resveratrol Inhibits the TRIF-Dependent Pathway by Upregulating Sterile Alpha and Armadillo Motif Protein, Contributing to Anti-Inflammatory Effects after Respiratory Syncytial Virus Infection
Authors: Liu Tiantian , Zang Na , Zhou Na , Li Wei , Xie Xiaohong , Deng Yu , Ren Luo , Long Xiaoru , Li Simin , Zhou Lili , Zhao Xiaodong , Tu Wenwei , Wang Lijia , Tan Bin , Liu Enmei 
Published: January 2014

ABSTRACT
Respiratory syncytial virus (RSV) is the most important cause of lower respiratory tract infection in young children and the leading cause of infant hospitalization worldwide. Uncontrolled response to RSV is mediated by a toll-like receptor (TLR)-mediated immune response. Resveratrol possesses anti-RSV activity and is an inhibitor of the TRIF/TBK1/IRF-3 complex. We hypothesize that resveratrol inhibits the TRIF-dependent pathway through upregulation of SARM post-RSV infection. BALB/c mice were infected with RSV and were injected with resveratrol 1 h postinoculation. SARM short interfering RNA was administered to RSV-infected and resveratrol-treated mice. Lung function was measured by whole-body plethysmography, lung histopathology was examined, and lymphocytes in bronchoalveolar lavage fluid were quantified. SARM and TRIF protein expression were detected in the lung by Western blot analyses. The expression of gamma interferon in bronchoalveolar lavage fluid (BALF) was evaluated by enzyme-linked immunosorbent assay (ELISA). SARM expression was reduced and TRIF expression was increased after infection with RSV. Resveratrol increased SARM expression and decreased TRIF expression after RSV infection. SARM knockdown in resveratrol-treated mice enhanced gamma interferon production, RSV-induced airway inflammation, and airway hyperresponsiveness (AHR). Resveratrol decreased TRIF expression and prevented the RSV-mediated reduction of SARM expression. Resveratrol-mediated inhibition of the TRIF-dependent pathway may be dependent on SARM expression.

IMPORTANCE
Our study provides insights into the regulation of innate immunity in response to RSV infection. The results suggest that resveratrol-mediated alterations in SARM have therapeutic potential against RSV immunopathology caused by deregulation of the TLR-mediated immune response. Ultimately, improved insight into the complex interplay between TLR adaptor proteins and the occurrence of severe RSV infection might lead to novel therapeutic treatment strategies, such as TLR adjuvants.
The Influenza A Virus Protein NS1 Displays Structural Polymorphism
Authors: Carrillo Berenice , Choi Jae-Mun , Bornholdt Zachary A. , Sankaran Banumathi , Rice Andrew P. , Prasad B. V. Venkataram 
Published: January 2014

ABSTRACT
NS1 of influenza A virus is a potent antagonist of host antiviral interferon responses. This multifunctional protein with two distinctive domains, an RNA-binding domain (RBD) and an effector domain (ED) separated by a linker region (LR), is implicated in replication, pathogenesis, and host range. Although the structures of individual domains of NS1 from different strains of influenza viruses have been reported, the only structure of full-length NS1 available to date is from an H5N1 strain (A/Vietnam/1203/2004). By carrying out crystallographic analyses of full-length H6N6-NS1 (A/blue-winged teal/MN/993/1980) and an LR deletion mutant, combined with mutational analysis, we show here that these full-length NS1 structures provide an exquisite structural sampling of various conformational states of NS1 that based on the orientation of the ED with respect to RBD can be summarized as “open,” “semi-open,” and “closed” conformations. Our studies show that preference for these states is clearly dictated by determinants such as linker length, residue composition at position 71, and a mechanical hinge, providing a structural basis for strain-dependent functional variations in NS1. Because of the flexibility inherent in the LR, any particular NS1 could sample the conformational space around these states to engage ED in different quaternary interactions so that it may participate in specific protein-protein or protein-RNA interactions to allow for the known multifunctionality of NS1. We propose that such conformational plasticity provides a mechanism for autoregulating NS1 functions, depending on its temporal distribution, posttranslational modifications, and nuclear or cellular localization, during the course of virus infection.

IMPORTANCE
NS1 of influenza A virus is a multifunctional protein associated with numerous strain-specific regulatory functions during viral infection, including conferring resistance to antiviral interferon induction, replication, pathogenesis, virulence, and host range. NS1 has two domains, an RNA-binding domain and an effector domain separated by a linker. To date, the only full-length NS1 structure available is that from an H5N1 strain (A/Vietnam/1203/2004). Here, we determined crystal structures of the wild type and a linker region mutant of the H6N6 NS1 (A/blue-winged teal/MN/993/1980), which together with the previously determined H5N1 NS1 structure show that NS1 exhibits significant strain-dependent structural polymorphism due to variations in linker length, residue composition at position 71, and a mechanical hinge. Such a structural polymorphism may be the basis for strain-specific functions associated with NS1.
Patterns of ALK expression in different human cancer types
Authors: Tennstedt Pierre , Strobel Gundula , Bölch Charlotte , Grob Tobias , Minner Sarah , Masser Sawinee , Simon Ronald 
Published: January 2014

AimsOncogenic gene fusions involving the anaplastic lymphoma kinase (ALK) tyrosine kinase have been identified in several haematopoietic and sporadically also in solid tumour types. Preliminary results from clinical trials suggest that patients with ALK fusion positive cancers might optimally benefit from the tyrosine kinase inhibitor crizotinib, but a comprehensive analysis of solid tumour types for ALK fusion and fusion associated expression is lacking.MethodsIn order to identify human solid cancers carrying ALK alterations, we performed real-time PCR screening of 1000 tumour samples representing 29 different tumour entities. ALK-positive samples were then transferred into a tissue microarray format and subjected to ALK break-apart fluorescence in situ hybridisation (FISH) analysis and ALK immunohistochemistry (IHC) analysis.ResultsALK expression was detected by real-time PCR in 260 of 896 (29%) interpretable tumour samples. FISH analysis was successful in 189 of 260 arrayed cancers but did not detect ALK rearrangement. There was also no ALK expression detectable by IHC.ConclusionsDifferent levels of ALK expression can be found in various cancer types using sensitive methods like real-time PCR. However, such low-level expression is independent from oncogenic ALK fusions and cannot be detected with less-sensitive methods like IHC. ALK fusion is a rare event in human solid cancers.
Flow behaviour in the intra-caldera setting: an AMS study of the large (>1290 km
3
) Permian Ora ignimbrite
Authors: Willcock Madelaine A. W. , Mattei Massimo , Hasalová Pavlína , Giordano Guido , Cas Ray A. F. , Morelli Corrado 
Published: January 2014

Abstract

Anisotropy of magnetic susceptibility (AMS) data reveal heterogeneous pyroclastic flow processes and variable flow directions within the intra-caldera setting of the Permian rhyolitic welded Ora ignimbrite. Magnetic fabric is primary, orientated during the pyroclastic flow emplacement, and is controlled by paramagnetic and ferromagnetic mineral phases. The ignimbrite has typically weak mean magnetic susceptibilities (1.32–21.8×10
−4
SI) but with a large spread and low anisotropy degrees (1.003–1.023), which vary in different parts of the caldera. The intra-caldera magnetic fabric provides significant information on the dynamics of the intra-caldera setting, relating to changing vertical and lateral flow emplacement processes. AMS shape ellipsoids range from oblate to prolate; these are interpreted to reflect the heterogeneous nature of the flow resulting from the influence of underlying topography, constraints of the caldera walls, primary welding and post-emplacement mineral growth. We have identified different depositional units and possible eruptive source regions, indicating that more than one source fissure vent was active during eruption within this caldera system. The lateral variations demonstrate a meandering of flow pulses. The caldera margin acts as an obstacle in preventing and rebuffing certain flows from scaling the caldera margin.
Expression of Variant Isoforms of the Tyrosine Kinase SYK Determines the Prognosis of Hepatocellular Carcinoma
Authors: Hong Jian , Yuan Yunfei , Wang Jianping , Liao Yadi , Zou Ruhai , Zhu Chuanlong , Li Binkui , Liang Yi , Huang Pinzhu , Wang Zongwei , Lin Wenyu , Zeng Yixin , Le Dai Jia , Chung Raymond T. 
Published: January 2014

Abstract
The spleen tyrosine kinase (SYK) has been reported as a novel biomarker for human hepatocellular carcinoma, but the functional contributions of its two isoforms SYK(L) and SYK(S) are undefined. In this study, we investigated their biologic functions and possible prognostic values in hepatocellular carcinoma. SYK(L) was downregulated in 38% of human specimens of hepatocellular carcinoma examined, whereas SYK(S) was detectable in 40% of these specimens but not in normal liver tissue samples without cirrhosis. SYK(S) expression correlated with pathologic parameters characteristic of tumor metastasis, including multiple tumors (P = 0.003) and vascular invasion (P = 0.001). Further, SYK(S) was specifically associated with epithelial–mesenchymal transition (EMT) in hepatocellular carcinoma specimens. Functional studies showed that SYK(S) promoted tumor growth, suppressed apoptosis, and induced EMT through the extracellular signal–regulated kinase pathway, countering the opposite effects of SYK(L). Patients with SYK(L+/S−) tumors exhibited longer overall survival and time to recurrence than those with SYK(L−/S−) or SYK(L+/S+) tumors (P &lt; 0.001). Taken together, our findings showed that SYK(S) enhances invasion, whereas SYK(L) inhibits metastasis in hepatocellular carcinoma. We suggest that SYK(L) downregulation or SYK(S) elevation are strong predictors of poor survival in patients with hepatocellular carcinoma, indicative of a need for aggressive therapeutic intervention. Cancer Res; 74(6); 1845–56. ©2014 AACR.
Consistency of thromboelastometry analysis under scrutiny: Results of a systematic evaluation within and between analysers
Authors: ten Cate Hugo , Kathriner Silvio , Casutt Mattias , Bachmann Lucas M. , Wuillemin Walter A. , Nagler Michael 
Published: January 2014

SummaryWhile the use of thromboelastometry analysis (ROTEM®) in evaluation of haemostasis is rapidly increasing, important validity parameters of testing remain inadequately examined. We aimed to study systematically the consistency of thromboelastometry parameters within individual tests regarding measurements between different analysers, between different channels of the same analyser, between morning and afternoon measurements (circadian variation), and if measured four weeks apart. Citrated whole blood samples from 40 healthy volunteers were analysed with two analysers in parallel. EXTEM, INTEM, FIBTEM, HEPTEM and APTEM tests were conducted. A Bland-Altman comparison was performed and homogeneity of variances was tested using the pitman test. P-value ranges were used to classify the level of homogeneity (p<0.15 – low homogeneity, p = 0.15 to 0.5 – intermediate homogeneity, p>0.5 high homogeneity). Less than half of all comparisons made showed high homogeneity of variances (p>0.5) and in about a fifth of comparisons data distributions were heterogeneous (p<0.15). There was no clear pattern for homogeneity. On average, comparisons of MCF, ML and LI30 measurements tended to be better, but none of the tests assessed outperformed another. In conclusion, systematic investigation reveals large differences in the results of some thromboelastometry parameters and lack of consistency. Clinicians and scientists should take these inconsistencies into account and focus on parameters with a higher homogeneity such as MCF.Note: Part of the investigation was presented at the 56th meeting of the “Gesellschaft für Thrombose- und Hämostaseforschung (GTH)” in St. Gallen, Switzerland, February 1–4, 2012.
Risk factors and prognostic impact of venous thromboembolism in Asian patients with non-small cell lung cancer
Authors: Lee Yun-Gyoo , Lee Eunyoung , Bang Soo-Mee , Kang Chang Hyun , Kim Young Tae , Kim Hak Jae , Wu Hong-Gyun , Kim Young Whan , Kim Tae Min , Lee Keun-Wook , Lee Se-Hoon , Kim Dong-Wan , Heo Dae Seog , Kim Inho 
Published: January 2014

SummaryAlthough the overall risk of venous thromboembolism (VTE) is high in patients with non-small cell lung cancer (NSCLC), risk identification is limited. The goal of this study was to estimate the incidence, risk factors and prognostic implications of VTE, and to evaluate a genetic link between oncogenes and the risk of VTE in Asian patients with NSCLC. A total of 1,998 consecutive patients with NSCLC were enrolled and analysed retrospectively. Since the effects of therapeutics on VTE development were modified by stage, stratified analyses were performed. When comparing overall survival in terms of VTE development, a propensity score-matching method was adopted to minimise potential confounding. The six-month and two-year cumulative incidences of VTE were 4.2% and 6.4%, respectively. The risk of VTE increased 2.45-fold with each advancing stage in NSCLC (p<0.001). The independent predictors of VTE were advanced age, pneumonectomy and palliative radiotherapy in localised NSCLC and ineligibility for surgery and palliative radiotherapy in locally advanced NSCLC. Adenocarcinoma histology (vs squamous cell) and former/current smoking status were significant predictors of VTE in metastatic NSCLC. A significant association between VTE and decreased survival was observed only among patients with localised NSCLC. EGFR mutations (p=0.170) and ALK rearrangements (p=0.159) were not associated with VTE development in lung adenocarcinoma. In conclusion, the two-year cumulative incidence of VTE is 6.4% in Asian patient with NSCLC. The significant predictors of VTE are different across stages of NSCLC. The prognostic impact of VTE on poor survival was limited to localised NSCLC.
Sildenafil Improves Exercise Hemodynamics in Fontan Patients
Authors: Van De Bruaene Alexander , La Gerche Andre , Claessen Guido , De Meester Pieter , Devroe Sarah , Gillijns Hilde , Bogaert Jan , Claus Piet , Heidbuchel Hein , Gewillig Marc , Budts Werner 
Published: January 2014

Background—
Patients with Fontan circulation have reduced exercise capacity. The absence of a presystemic pump may limit flow through the pulmonary circulation, restricting ventricular filling and cardiac output. We evaluated exercise hemodynamics and the effect of sildenafil on exercise hemodynamics in Fontan patients.

Methods and Results—

Ten Fontan patients (6 men, 20±4 years) underwent cardiac magnetic resonance imaging at rest and during supine bicycle exercise before and after sildenafil. Systemic ventricular volumes were obtained at rest and during low- (34±15 W), moderate- (69±29 W), and high-intensity (97±36 W) exercise using an ungated, free-breathing cardiac magnetic resonance sequence and analyzed correcting for cardiac phase and respiratory translation. Radial and pulmonary artery pressures and cGMP were measured. Before sildenafil, cardiac index increased throughout exercise (4.0±0.9, 5.9±1.1, 7.0±1.6, 7.4±1.7 L/(min·m
2
);
P
<0.0001) with 106±49% increase in heart rate. Stroke volume index (
P
=0.015) and end-diastolic volume index (
P
=0.001) decreased during exercise. End-systolic volume index remained unchanged (
P
=0.8). Total pulmonary resistance index (
P
=0.005) increased, whereas systemic vascular resistance index decreased during exercise (
P
<0.0001). Sildenafil increased cardiac index (
P
<0.0001) and stroke volume index (
P
=0.003), especially at high-intensity exercise (interaction
P
=0.004 and
P
=0.003, respectively). Systemic vascular resistance index was reduced (
P
<0.0001–interaction
P
=0.1), whereas total pulmonary resistance index was reduced at rest and reduced further during exercise (
P
=0.008–interaction
P
=0.029). cGMP remained unchanged before sildenafil (
P
=0.9), whereas it increased significantly after sildenafil (
P
=0.019).

Conclusions—
In Fontan patients, sildenafil improved cardiac index during exercise with a decrease in total pulmonary resistance index and an increase in stroke volume index. This implies that pulmonary vasculature represents a physiological limitation, which can be attenuated by sildenafil, the clinical significance of which warrants further study.
Taxonomic study of Chinese species of the genus Macropsis Lewis, 1836 (Hemiptera: Cicadellidae: Macropsinae) III: a review of oak-dwelling species
Authors: LI HU , TISHECHKIN DMITRI YU. , DAI REN-HUAI , LI ZI-ZHONG 
Published: February 2014

The group of Chinese Macropsis species dwelling on oak (Quercus spp.) is reviewed and nine species are recognized. Among them, three new species, Macropsis huangbana sp. nov. from Shaanxi and Yunnan Provinces, M. latiprocessa sp. nov. from Guizhou Province and M. longiprocessa sp. nov. from Yunnan Province, are described and illustrated; M. irenae Viraktamath, 1981 (= M. irrorata Tishechkin, 2002, nec Matsumura, 1912) is recorded from China and Japan for the first time; M. meifengensis Huang & Viraktamath, 1993 and M. jozankeana (Matsumura, 1912) are redescribed based on examination of specimens from mainland China and adjacent territories of Russia respectively; translation of the original description of M. rubrosternalis Kuoh, 1992 from Chinese is provided, also a key to species of Oak-dwelling Macropsis from China is present.
Reynolds Stress and Eddy Diffusivity of β-Plane Shear Flows
Authors: Srinivasan Kaushik , Young W. R. 
Published: February 2014

Abstract
The Reynolds stress induced by anisotropically forcing an unbounded Couette flow, with uniform shear γ, on a β plane, is calculated in conjunction with the eddy diffusivity of a coevolving passive tracer. The flow is damped by linear drag on a time scale μ−1. The stochastic forcing is white noise in time and its spatial anisotropy is controlled by a parameter α that characterizes whether eddies are elongated along the zonal direction (α &lt; 0), are elongated along the meridional direction (α &gt; 0), or are isotropic (α = 0). The Reynolds stress varies linearly with α and nonlinearly and nonmonotonically with γ, but the Reynolds stress is independent of β. For positive values of α, the Reynolds stress displays an “antifrictional” effect (energy is transferred from the eddies to the mean flow); for negative values of α, it displays a frictional effect. When γ/μ ≪ 1, these transfers can be identified as negative and positive eddy viscosities, respectively. With γ = β = 0, the meridional tracer eddy diffusivity is , where υ′ is the meridional eddy velocity. In general, nonzero β and γ suppress the eddy diffusivity below . When the shear is strong, the suppression due to γ varies as γ−1 while the suppression due to β varies between β−1 and β−2 depending on whether the shear is strong or weak, respectively.
Low-Level Cloud Response to the Gulf Stream Front in Winter Using CALIPSO*
Authors: Liu Jing-Wu , Xie Shang-Ping , Norris Joel R. , Zhang Su-Ping 
Published: January 2014

Abstract
A sharp sea surface temperature front develops between the warm water of the Gulf Stream and cold continental shelf water in boreal winter. This front has a substantial impact on the marine boundary layer. The present study analyzes and synthesizes satellite observations and reanalysis data to examine how the sea surface temperature front influences the three-dimensional structure of low-level clouds. The Cloud–Aerosol Lidar and Infrared Pathfinder Satellite Observations (CALIPSO) satellite captures a sharp low-level cloud transition across the Gulf Stream front, a structure frequently observed under the northerly condition. Low-level cloud top (&lt;4 km) increases by about 500 m from the cold to the warm flank of the front. The sea surface temperature front induces a secondary low-level circulation through sea level pressure adjustment with ascending motion over the warm water and descending motion over cold water. The secondary circulation further contributes to the cross-frontal transition of low-level clouds. Composite analysis shows that surface meridional advection over the front plays an important role in the development of the marine atmospheric boundary layer and low-level clouds. Under cold northerly advection over the Gulf Stream front, strong near-surface instability leads to a well-mixed boundary layer over the Gulf Stream, causing southward deepening of low-level clouds across the sea surface temperature front. Moreover, the front affects the freezing level by transferring heat to the atmosphere and therefore influences the cross-frontal variation of the cloud phase.
Seasonal Prediction of Regional Reference Evapotranspiration Based on Climate Forecast System Version 2
Authors: Tian Di , Martinez Christopher J. , Graham Wendy D. 
Published: February 2014

AbstractReference evapotranspiration (ETo) is an important hydroclimatic variable for water planning and management. This research explored the potential of using the Climate Forecast System, version 2 (CFSv2), for seasonal predictions of ETo over the states of Alabama, Georgia, and Florida. The 12-km ETo forecasts were produced by downscaling coarse-scale ETo forecasts from the CFSv2 retrospective forecast archive and by downscaling CFSv2 maximum temperature (Tmax), minimum temperature (Tmin), mean temperature (Tmean), solar radiation (Rs), and wind speed (Wind) individually and calculating ETo using those downscaled variables. All the ETo forecasts were calculated using the Penman–Monteith equation. Sensitivity coefficients were evaluated to quantify how and how much does each of the variables influence ETo. Two statistical downscaling methods were tested: 1) spatial disaggregation (SD) and 2) spatial disaggregation with quantile mapping bias correction (SDBC). The downscaled ETo from the coarse-scale ETo showed similar skill to those by first downscaling individual variables and then calculating ETo. The sensitivity coefficients showed Tmax and Rs had the greatest influence on ETo, followed by Tmin and Tmean, and Wind. The downscaled Tmax showed highest predictability, followed by Tmean, Tmin, Rs, and Wind. SDBC had slightly better performance than SD for both probabilistic and deterministic forecasts. The skill was locally and seasonally dependent. The CFSv2-based ETo forecasts showed higher predictability in cold seasons than in warm seasons. The CFSv2 model could better predict ETo in cold seasons during El Niño–Southern Oscillation (ENSO) events only when the forecast initial condition was in either the El Niño or La Niña phase of ENSO.