bluuebunny/crossref_metadata_2025_split huggingface dataset:
TRIM5α Degradation via Autophagy Is Not Required for Retroviral Restriction
Authors: Imam Sabrina , Talley Sarah , Nelson Rachel S. , Dharan Adarsh , O'Connor Christopher , Hope Thomas J. , Campbell Edward M. 
Published: January 2016

ABSTRACT
TRIM5α is an interferon-inducible retroviral restriction factor that prevents infection by inducing the abortive disassembly of capsid cores recognized by its C-terminal PRY/SPRY domain. The mechanism by which TRIM5α mediates the disassembly of viral cores is poorly understood. Previous studies demonstrated that proteasome inhibitors abrogate the ability of TRIM5α to induce premature core disassembly and prevent reverse transcription; however, viral infection is still inhibited, indicating that the proteasome is partially involved in the restriction process. Alternatively, we and others have observed that TRIM5α associates with proteins involved in autophagic degradation pathways, and one recent study found that autophagic degradation is required for the restriction of retroviruses by TRIM5α. Here, we show that TRIM5α is basally degraded via autophagy in the absence of restriction-sensitive virus. We observe that the autophagy markers LC3b and lysosome-associated membrane protein 2A (LAMP2A) localize to a subset of TRIM5α cytoplasmic bodies, and inhibition of lysosomal degradation with bafilomycin A1 increases this association. To test the requirement for macroautophagy in restriction, we examined the ability of TRIM5α to restrict retroviral infection in cells depleted of the autophagic mediators ATG5, Beclin1, and p62. In all cases, restriction of retroviruses by human TRIM5α, rhesus macaque TRIM5α, and owl monkey TRIM-Cyp remained potent in cells depleted of these autophagic effectors by small interfering RNA (siRNA) knockdown or clustered regularly interspaced short palindromic repeat (CRISPR)-Cas9 genome editing. Collectively, these results are consistent with observations that the turnover of TRIM5α proteins is sensitive to autophagy inhibition; however, the data presented here do not support observations that the inhibition of autophagy abrogates retroviral restriction by TRIM5 proteins.

IMPORTANCE
Restriction factors are a class of proteins that inhibit viral replication. Following fusion of a retrovirus with a host cell membrane, the retroviral capsid is released into the cytoplasm of the target cell. TRIM5α inhibits retroviral infection by promoting the abortive disassembly of incoming retroviral capsid cores; as a result, the retroviral genome is unable to traffic to the nucleus, and the viral life cycle is extinguished. In the process of restriction, TRIM5α itself is degraded by the proteasome. However, in the present study, we have shown that in the absence of a restriction-sensitive virus, TRIM5α is degraded by both proteasomal and autophagic degradation pathways. Notably, we observed that restriction of retroviruses by TRIM5α does not require autophagic machinery. These data indicate that the effector functions of TRIM5α can be separated from its degradation and may have further implications for understanding the mechanisms of other TRIM family members.
Acidianus Tailed Spindle Virus: a New Archaeal Large Tailed Spindle Virus Discovered by Culture-Independent Methods
Authors: Hochstein Rebecca A. , Amenabar Maximiliano J. , Munson-McGee Jacob H. , Boyd Eric S. , Young Mark J. 
Published: January 2016

ABSTRACTThe field of viral metagenomics has expanded our understanding of viral diversity from all three domains of life (Archaea,Bacteria, andEukarya). Traditionally, viral metagenomic studies provide information about viral gene content but rarely provide knowledge about virion morphology and/or cellular host identity. Here we describe a new virus,Acidianustailed spindle virus (ATSV), initially identified by bioinformatic analysis of viral metagenomic data sets from a high-temperature (80°C) acidic (pH 2) hot spring located in Yellowstone National Park, followed by more detailed characterization using only environmental samples without dependency on culturing. Characterization included the identification of the large tailed spindle virion morphology, determination of the complete 70.8-kb circular double-stranded DNA (dsDNA) viral genome content, and identification of its cellular host. Annotation of the ATSV genome revealed a potential three-domain gene product containing an N-terminal leucine-rich repeat domain, followed by a likely posttranslation regulatory region consisting of high serine and threonine content, and a C-terminal ESCRT-III domain, suggesting interplay with the host ESCRT system. The host of ATSV, which is most closely related toAcidianus hospitalis, was determined by a combination of analysis of cellular clustered regularly interspaced short palindromic repeat (CRISPR)/Cas loci and dual viral and cellular fluorescencein situhybridization (viral FISH) analysis of environmental samples and confirmed by culture-based infection studies. This work provides an expanded pathway for the discovery, isolation, and characterization of new viruses using culture-independent approaches and provides a platform for predicting and confirming virus hosts.IMPORTANCEVirus discovery and characterization have been traditionally accomplished by using culture-based methods. While a valuable approach, it is limited by the availability of culturable hosts. In this research, we report a virus-centered approach to virus discovery and characterization, linking viral metagenomic sequences to a virus particle, its sequenced genome, and its host directly in environmental samples, without using culture-dependent methods. This approach provides a pathway for the discovery, isolation, and characterization of new viruses. While this study used an acidic hot spring environment to characterize a new archaeal virus,Acidianustailed spindle virus (ATSV), the approach can be generally applied to any environment to expand knowledge of virus diversity in all three domains of life.
Bacterial Transcription as a Target for Antibacterial Drug Development
Authors: Ma Cong , Yang Xiao , Lewis Peter J. 
Published: January 2016

SUMMARY
Transcription, the first step of gene expression, is carried out by the enzyme RNA polymerase (RNAP) and is regulated through interaction with a series of protein transcription factors. RNAP and its associated transcription factors are highly conserved across the bacterial domain and represent excellent targets for broad-spectrum antibacterial agent discovery. Despite the numerous antibiotics on the market, there are only two series currently approved that target transcription. The determination of the three-dimensional structures of RNAP and transcription complexes at high resolution over the last 15 years has led to renewed interest in targeting this essential process for antibiotic development by utilizing rational structure-based approaches. In this review, we describe the inhibition of the bacterial transcription process with respect to structural studies of RNAP, highlight recent progress toward the discovery of novel transcription inhibitors, and suggest additional potential antibacterial targets for rational drug design.
FABRICATION AND WEAR BEHAVIOR ANALYSIS ON AlCrFeNi HIGH ENTROPY ALLOY COATING UNDER DRY SLIDING AND OIL LUBRICATION TEST CONDITIONS
Authors: TANG YIPIN , WANG SHOUREN , SUN BIN , WANG YAN , QIAO YANG 
Published: January 2016

In this paper, AlCrFeNi high entropy alloy coating was fabricated on the surface of Q235 steel using hot pressing sintering process. The coating has the controlled thickness size and excellent mechanical properties. Scanning electron microscopy (SEM), XRD and hardness testing method were used to study the morphology, phase structure and hardness of high entropy alloys coating. The lattice distortion plays a significant role in increasing the hardness. Coating formation mechanism caused by the element diffusion under the hot pressing effect is also discussed in the paper. Simultaneously, the dry sliding and oil lubrication wear tests, wear morphology observation and wear mechanism discussion were completed. As the result shows, AlCrFeNi high entropy alloys coating exhibits superior wear resistance either at dry sliding or oil lubrication tests owing to its hard high entropy solid solution structure.
Magnified Damping Under Rashba Spin–Orbit Coupling
Authors: Tan Seng Ghee , Jalil Mansoor B. A. 
Published: January 2016

The spin–orbit coupling spin torque consists of the field-like [S. G. Tan et al., arXiv:0705.3502 (2007).] and the damping-like terms [H. Kurebayashi et al., Nat. Nanotechnol. 9, 211 (2014).] that have been widely studied for applications in magnetic memory. We focus, in this paper, not on the spin–orbit effect producing the above spin torques, but on its magnifying the damping constant of all field-like spin torques. As first-order precession leads to second-order damping, the Rashba constant is naturally co-opted, producing a magnified field-like damping effect. The Landau–Liftshitz–Gilbert equations are written separately for the local magnetization and the itinerant spin, allowing the progression of magnetization to be self-consistently locked to the spin.
Late Antique marble trade: new insights obtained from stone artefacts from the San Severo complex (Ravenna, Italy)
Authors: Tůmová Helena , Augenti Andrea , Kuchařová Aneta , Cirelli Enrico , Přikryl Richard 
Published: January 2016

Abstract
Ravenna represented an important administrative, commercial and cultural centre in the fifth and sixth centuries. The present study explored the commercial mechanisms of Ravenna in Late Antiquity from the point of view of the marble trade, as well as the trade in other architectural elements. A portion of the research is based on the macroscopic and quantitative study of stone materials (around 1000 fragments) from the Late Antique and medieval complex of San Severo in Classe (Ravenna, Italy). The results indicated that the predominant commercial relationships of Ravenna with respect to stone artefacts (marbles, limestones, porphyry, breccia, granites) were orientated mainly towards the regions of Asia Minor, with some trade also occurring in minor quantities with North Africa, Greece, Italy, and France.
Three representative marble samples were analysed to make determinations of their provenance. The methods used were based upon a combination of petrographic image analysis, polarizing and cathodoluminescence microscopy of thin sections, and stable isotope geochemistry of carbonates. The Proconnesos and, eventually, other Turkish provenance of the selected samples is considered.
Constraints on melt distribution from seismology: a case study in Ethiopia
Authors: Hammond J. O. S. , Kendall J.-M. 
Published: January 2016

Abstract
Low seismic velocities and/or strong seismic anisotropy are often interpreted as being caused by partial melt. To better understand this, we used numerical modelling, varying the shape and amount of melt, to show how seismic phases are affected by melt. We observed that seismic waves are more sensitive to the shape than to the amount of melt. Rayleigh wave velocities were almost always reduced in the presence of melt, while Pn/wide-angle P-wave refraction and Love wave velocities showed low velocity anomalies for vertically aligned melt, but little anomaly for horizontally aligned melt. These data can therefore be used to determine the alignment of melt. Shear wave splitting/receiver functions showed strong anisotropy and can be used to constrain the strike of vertically aligned partial melt. We showed that melt in the mantle beneath Ethiopia is probably stored in low aspect ratio disc-like inclusions, suggesting that the melt is not in textural equilibrium. We estimated that 2–7% of the vertically aligned melt is stored beneath the Main Ethiopian Rift, >6% of the horizontally and vertically aligned melt is stored beneath the Red Sea Rift and 1–6% of the horizontally aligned melt is stored beneath the Danakil microplate. This supports the idea of strong shear-derived segregation of melt in the narrow Main Ethiopian Rift compared with that observed beneath Afar.
T-Cell Immunoglobulin and ITIM Domain (TIGIT) Associates with CD8+ T-Cell Exhaustion and Poor Clinical Outcome in AML Patients
Authors: Kong Yaxian , Zhu Liuluan , Schell Todd D. , Zhang Jianhong , Claxton David F. , Ehmann W. Christopher , Rybka Witold B. , George Melissa R. , Zeng Hui , Zheng Hong 
Published: January 2016

Abstract
Purpose: T-cell immunoglobulin and immunoreceptor tyrosine–based inhibitory motif (ITIM) domain (TIGIT) is a recently identified T-cell coinhibitory receptor. In this study, we aimed to determine the clinical impact of TIGIT in patients with acute myelogenous leukemia (AML) and dissect the role of TIGIT in the pathogenesis of leukemia progression.
Experimental Design: TIGIT expression on T cells from peripheral blood collected from patients with AML was examined by flow cytometry. The correlation of TIGIT expression to clinical outcomes, including rate of complete remission and relapse post-allogeneic stem cell transplantation (alloSCT) in AML patients, was analyzed. Phenotypic and functional study (cytokine release, proliferation, killing, and apoptosis) of TIGIT-expressing T cells were performed. Using siRNA to silence TIGIT, we further elucidated the regulatory role of TIGIT in the T-cell immune response by dissecting the effect of TIGIT knockdown on cytokine release and apoptosis of T cells from AML patients.
Results: TIGIT expression on CD8+ T cells is elevated in AML patients and high-TIGIT correlates with primary refractory disease and leukemia relapse post-alloSCT. TIGIT+ CD8+ T cells display phenotypic features of exhaustion and exhibit functional impairment manifested by low production of cytokines and high susceptibility to apoptosis. Importantly, their functional defects are reversed by TIGIT knockdown.
Conclusions: TIGIT contributes to functional T-cell impairment and associates with poor clinical outcome in AML. Our study suggests that blockade of TIGIT to restore T-cell function and antitumor immunity may represent a novel effective leukemia therapeutic. Clin Cancer Res; 22(12); 3057–66. ©2016 AACR.
Tissue factor associates with survival and regulates tumour progression in osteosarcoma
Authors: Tieken Chris , Verboom Michiel C. , Ruf Wolfram , Gelderblom Hans , Bovée Judith V. M. G. , Reitsma Pieter H. , Cleton-Jansen Anne-Marie , Versteeg Henri H. 
Published: January 2016

SummaryOsteosarcoma is the most common primary malignant bone tumour. Patients often develop lung metastasis and have a poor prognosis despite extensive chemotherapy and surgical resections. Tissue Factor is associated with poor clinical outcome in a wide range of cancer types, and promotes angiogenesis and metastasis. The role of Tissue Factor in OS tumourigenesis is unknown. Fifty-three osteosarcoma pre-treatment biopsies and four osteosarcoma cell lines were evaluated for Tissue Factor expression, and a possible association with clinical parameters was investigated. Tissue Factor function was inhibited in an osteosarcoma cell line (143B) by shRNA knockdown or specific antibodies, and pro-tumourigenic gene expression, proliferation, matrigel invasion and transwell migration was examined. 143B cells were implanted in mice in the presence of Tissue Factor-blocking antibodies, and tumour volume, micro-vessel density and metastases in the lung were evaluated. Tissue Factor was highly expressed in 73.6 % of osteosarcoma biopsies, and expression associated significantly with disease-free survival. Tissue Factor was expressed in all four investigated cell lines. Tissue Factor was knocked down in 143B cells, which led to reduced expression of IL-8, CXCL-1, SNAIL and MMP2, but not MMP9. Tissue Factor knockdown or inhibition with antibodies reduced matrigel invasion. Tissue Factor antibodies limited 143B tumour growth in vivo, and resulted in decreased intra-tumoural micro-vessel density. Furthermore, lung metastasis from the primary tumour was significantly reduced. Thus, Tissue Factor expression in osteosarcoma reduces metastasis-free survival in patients, and increases pro-tumourigenic behaviour both in vitro and in vivo.Supplementary Material to this article is available online at www.thrombosis-online.com.
Maré sitiada: o discurso midiático sobre a ocupação militar do Complexo da Maré
Authors: Souza Renata Da Silva 
Published: January 2016

<p>A Maré, conjunto de favelas localizado na zona norte do Rio de Janeiro, foi ocupada em abril de 2014 por forças militares de pacificação, engenhosa operação que envolveu um total de 2.700 militares com 20 tanques blindados. Assim, este artigo toma como objeto a cobertura midiática da ocupação militar, utilizando como método a análise das reportagens publicadas em tempo real durante a invasão. A ideia é esboçar as tensões entre o discurso dos meios de comunicação e as estratégias informativas engendradas nas redes sociais por narradores comunitários da Maré. Tais iniciativas podem colocar em disputa novas versões dos fatos. Serão traçadas abordagens teóricas que deem conta da análise a respeito da ordem do discurso, a partir de Foucault e de uma breve reflexão sobre o discurso do sofrimento.</p>
Prognosis of Myocardial Damage in Sarcoidosis Patients With Preserved Left Ventricular Ejection Fraction
Authors: Murtagh Gillian , Laffin Luke J. , Beshai John F. , Maffessanti Francesco , Bonham Catherine A. , Patel Amit V. , Yu Zoe , Addetia Karima , Mor-Avi Victor , Moss Joshua D. , Hogarth D. Kyle , Sweiss Nadera J. , Lang Roberto M. , Patel Amit R. 
Published: January 2016

Background—
Cardiac sarcoidosis is associated with an increased risk of heart failure and sudden death, but its risk in patients with preserved left ventricular ejection fraction is unknown. Using cardiovascular magnetic resonance in patients with extracardiac sarcoidosis and preserved left ventricular ejection fraction, we sought to (1) determine the prevalence of cardiac sarcoidosis or associated myocardial damage, defined by the presence of late gadolinium enhancement (LGE), (2) quantify their risk of death/ventricular tachycardia (VT), and (3) identify imaging-based covariates that predict who is at greatest risk of death/VT.

Methods and Results—

Parameters of left and right ventricular function and LGE burden were measured in 205 patients with left ventricular ejection fraction >50% and extracardiac sarcoidosis who underwent cardiovascular magnetic resonance for LGE evaluation. The association between covariates and death/VT in the entire group and within the LGE+ group was determined using Cox proportional hazard models and time-dependent receiver–operator curves analysis. Forty-one of 205 patients (20%) had LGE; 12 of 205 (6%) died or had VT during follow-up; of these, 10 (83%) were in the LGE+ group. In the LGE+ group (1) the rate of death/VT per year was >20× higher than LGE− (4.9 versus 0.2%,
P
<0.01); (2) death/VT were associated with a greater burden of LGE (14±11 versus 5±5%,
P
<0.01) and right ventricular dysfunction (right ventricular EF 45±12 versus 53±28%,
P
=0.04). LGE burden was the best predictor of death/VT (area under the receiver-operating characteristics curve, 0.80); for every 1% increase of LGE burden, the hazard of death/VT increased by 8%.

Conclusions—
Sarcoidosis patients with LGE are at significant risk for death/VT, even with preserved left ventricular ejection fraction. Increased LGE burden and right ventricular dysfunction can identify LGE+ patients at highest risk of death/VT.
Effect of Intensive Versus Usual Blood Pressure Control on Kidney Function Among Individuals With Prior Lacunar Stroke
Authors: Peralta Carmen A. , McClure Leslie A. , Scherzer Rebecca , Odden Michelle C. , White Carole L. , Shlipak Michael , Benavente Oscar , Pergola Pablo 
Published: January 2016

Background—
The effect of intensive blood pressure (BP) lowering on kidney function among individuals with established cerebrovascular disease and preserved estimated glomerular filtration rate (eGFR) is not established.

Methods and Results—

Among 2610 participants randomized to a lower (<130 mm Hg) versus higher (130–149 mm Hg) systolic BP target with repeated measures of serum creatinine, we evaluated differences by study arm in annualized eGFR decline and rapid decline (eGFR decline >30%) using linear mixed models and logistic regression, respectively. We assessed associations of both treatment and kidney function decline with stroke, major vascular events, and the composite of stroke, death, major vascular events, or myocardial infarction using multivariable Cox regression, separately and jointly including a test for interaction. Analyses were conducted by treatment arm. Mean age was 63±11 years; 949 participants (36%) were diabetic; and mean eGFR was 80±19 mL·min
−1
·1.73 m
−2
. At 9 months, achieved systolic BP was 137±15 versus 127±14 mm Hg in the higher versus lower BP group, and differences were maintained throughout follow-up (mean, 3.2 years). Compared with the higher target, the lower BP target had a −0.50–mL·min
−1
·1.73 m
−2
per year (95% confidence interval [CI], −0.79 to −0.21) faster eGFR decline. Differences were most pronounced during the first year (−2.1 mL·min
−1
·1.73 m
−2
; 95% CI, −0.97 to −3.2), whereas rates of eGFR decline did not differ after year 1 (−0.095; 95% CI, −0.47 to 0.23). A total of 313 patients (24%) in the lower BP group had rapid kidney function decline compared with 247 (19%) in the higher BP group (odds ratio, 1.4; 95% CI, 1.1–1.6). Differences in rapid decline by treatment arm were apparent in the first year (odds ratio, 1.4; 95% CI, 1.1–1.8) but were not significant after year 1 (odds ratio, 1.0; 95% CI, 0.73–1.4). Rapid decline was associated with higher risk for stroke, major vascular events, and composite after full adjustment among individuals randomized to the higher BP target (stroke hazard ratio, 1.93; 95% CI, 1.15–3.21) but not the lower BP arm (stroke hazard ratio, 0.93; 95% CI, 0.50–1.75; all
P
for interaction <0.06).

Conclusions—
In patients with prior lacunar stroke and relatively preserved kidney function, intensive BP lowering was associated with a greater likelihood of rapid kidney function decline. Differences were observed primarily during the first year of antihypertensive treatment. Rapid kidney function decline was not associated with increased risk for clinical events among those undergoing intensive BP lowering.

Clinical Trial Registration—

URL:
http://www.clinicalTrials.gov
. Unique identifier: NCT00059306.