bluuebunny/crossref_metadata_2025_split huggingface dataset:
Staufen-1 Interacts with the Human Endogenous Retrovirus Family HERV-K(HML-2) Rec and Gag Proteins and Increases Virion Production
Authors: Hanke Kirsten , Hohn Oliver , Liedgens Linda , Fiddeke Katharina , Wamara Jula , Kurth Reinhard , Bannert Norbert 
Published: August 2013

ABSTRACT
The human endogenous retrovirus family HERV-K(HML-2) Rec protein is an RNA transport factor that enhances nuclear export of intron-containing retroviral transcripts. Using the yeast two-hybrid approach, we have newly identified human Staufen-1 as a Rec-interacting protein. The interaction was confirmed by coimmunoprecipitation experiments, and the relevant site in Staufen-1 has been mapped to double-stranded RNA binding domain 4 (RBD4). Staufen-1 is in several aspects functionally related to retroviral RNA transport proteins. It binds mRNAs and targets its ribonuclear cargo to polysomes for efficient translation. We observed an accumulation of Staufen-1 in the nucleus of Rec-expressing cells and colocalization in the nucleoli as well as in the cytoplasm. Overexpression of Staufen-1 resulted in a 5-fold enhancement in nuclear export and/or translation of unspliced HERV-K(HML-2) viral RNAs in the presence of Rec and its Rec-responsive element (RcRE) binding site together with a clear increase in virus production. Staufen-1 was previously shown to interact with the Gag protein of HIV-1, promoting Gag oligomerization and RNA encapsidation. We demonstrate here that Staufen-1 also binds to the Gag protein of HERV-K(HML-2). Under stress conditions, Rec colocalizes with Staufen-1 in stress granules in cells that express viral RNA but not in mRNA-decay-related processing bodies. Our results suggest a new role for Staufen-1 as a cellular Rec and HERV-K(HML-2) Gag cofactor.
Modern management of acute non-variceal upper gastrointestinal bleeding
Authors: Hegade Vinod S , Sood Ruchit , Mohammed Noor , Moreea Sulleman 
Published: August 2013

Abstract
An acute upper gastrointestinal bleed (AUGIB) often represents a life-threatening event and is recognised universally as a common cause of emergency hospitalisation. Large observational studies have improved our understanding of the disease characteristics and its impact on mortality but despite significant advancement in endoscopic management, mortality remains high, particularly in elderly patients and those with multiple comorbidities. Skilled assessment, risk stratification and prompt resuscitation are essential parts of patient care, with endoscopy playing a key role in the definitive management. A successful outcome partly relies on the clinician's familiarity with current guidelines and recommendations, including the National Institute for Clinical Excellence guidelines published in 2012. Validated risk stratification scores, such as the Blatchford and Rockall score, facilitate early discharge of low-risk patients as well as help in identifying those needing early endoscopic intervention. Major advances in therapeutic endoscopy, including more recently, the development of non-toxic proprietary powders (Hemospray and EndoClot), have resulted in the development of effective treatments of bleeding lesions, reduction in rebleeding rates and the need for emergency surgery. The role of proton-pump inhibitor therapy prior to endoscopy and the level of optimum red cell transfusion in the setting of AUGIB remain fields that require further research.
Automated forensic soil mineral analysis; testing the potential of lithotyping
Authors: Pirrie Duncan , Rollinson Gavyn K. , Power Matthew R. , Webb Julia 
Published: August 2013

Abstract
In the investigation of serious crimes, soil can be, in some cases, a very valuable class of trace evidence. The complexity of soil is part of the reason why it is useful as trace evidence but is also an inherent problem, as there are many different parameters in a soil sample that could potentially be characterized. The inorganic components of soils are dominated by minerals, along with anthropogenic particulate grains; thus, the analysis of soil mineralogy as the main technique for inorganic forensic soil characterization is recommended. Typical methods that allow the bulk mineralogy to be determined, such as X-ray diffraction (XRD), do not allow the texture of the particles to be characterized. However, automated scanning electron microscopy (SEM) provides both modal mineralogy and also allows particle textures to be characterized. A recent advance in this technique has been the ability to report the modal mineralogy of a sample as ‘lithotypes’, which are defined on the basis of a combination of mineralogy and other parameters, such as grain size and mineral associations. Defined lithotype groups may include monominerallic grains but also, importantly, allow the automated quantification of rock types and other anthropogenic materials. Based on a simulated forensic scenario, the use of lithotyping is evaluated as an aid in the analysis of soil samples. This technique provides additional discrimination when comparing different soil samples.
Differential Induction of Apoptosis and Senescence by the DNA Methyltransferase Inhibitors 5-Azacytidine and 5-Aza-2′-Deoxycytidine in Solid Tumor Cells
Authors: Venturelli Sascha , Berger Alexander , Weiland Timo , Essmann Frank , Waibel Michaela , Nuebling Tina , Häcker Sabine , Schenk Martin , Schulze-Osthoff Klaus , Salih Helmut R. , Fulda Simone , Sipos Bence , Johnstone Ricky W. , Lauer Ulrich M. , Bitzer Michael 
Published: August 2013

Abstract
Epigenetic alterations are a hallmark of cancer that govern the silencing of genes. Up to now, 5-azacytidine (5-aza-CR, Vidaza) and 5-aza-2′-deoxycytidine (5-aza-dC, Dacogen) are the only clinically approved DNA methyltransferase inhibitors (DNMTi). Current effort tries to exploit DNMTi application beyond acute leukemia or myelodysplastic syndrome, especially to solid tumors. Although both drugs only differ by a minimal structural difference, they trigger distinct molecular mechanisms that are highly relevant for a rational choice of new combination therapies. Therefore, we investigated cell death pathways in vitro in human hepatoma, colon, renal, and lung cancer cells and in vivo in chorioallantoic membrane and xenograft models. Real-time cancer cell monitoring and cytokine profiling revealed a profoundly distinct response pattern to both drugs. 5-aza-dC induced p53-dependent tumor cell senescence and a high number of DNA double-strand breaks. In contrast, 5-aza-CR downregulated p53, induced caspase activation and apoptosis. These individual response patterns of tumor cells could be verified in vivo in chorioallantoic membrane assays and in a hepatoma xenograft model. Although 5-aza-CR and 5-aza-dC are viewed as drugs with similar therapeutic activity, they induce a diverse molecular response in tumor cells. These findings together with other reported differences enable and facilitate a rational design of new combination strategies to further exploit the epigenetic mode of action of these two drugs in different areas of clinical oncology. Mol Cancer Ther; 12(10); 2226–36. ©2013 AACR.
Myeloid TGF-β Responsiveness Promotes Metastases
Authors: Souza-Fonseca-Guimaraes Fernando , Smyth Mark J. 
Published: August 2013

Abstract
Summary: Tumor-induced immune suppression is a major impediment to many potentially effective cancer therapies. TGF-β has previously been described as having both tumor-promoting and tumor-suppressive characteristics. In this issue of Cancer Discovery, Pang and colleagues show that myeloid-specific TGF-β signaling is a critical mediator in tumor metastasis. These findings point to a more specific means to reduce cancer immunosuppression, prevent metastasis, and minimize treatment-related adverse events. Cancer Discov; 3(8); 846–8. ©2013 AACR.
See related article by Pang et al., p. 936
Targeting BRAF in Multiple Myeloma
Authors: O'Donnell Elizabeth , Raje Noopur S. 
Published: August 2013

Abstract
Summary: In multiple myeloma, it is believed that multiple mutations in different pathways deregulate the intrinsic biology of the plasma cell, resulting in a genetically complex heterogeneous disease. Mutations in the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway have been identified and represent potential targets for therapy in this disease. BRAF, a serine/threonine kinase, has received considerable attention given the success of targeted therapy in malignant melanoma. Andrulis and colleagues report, for the first time, successful treatment of multiple myeloma with vemurafenib, a BRAF inhibitor, in a patient with a BRAF mutation. Cancer Discov; 3(8); 840–2. ©2013 AACR.
See related article by Andrulis et al., p. 862
Exchange of extracellular domains of CCR1 and CCR5 reveals confined functions in CCL5-mediated cell recruitment
Authors: Kramp Birgit K. , Megens Remco T. A. , Sarabi Alisina , Winkler Sabine , Projahn Delia , Weber Christian , Koenen Rory R. , von Hundelshausen Philipp 
Published: August 2013

SummaryThe chemokine CCL5 recruits monocytes into inflamed tissues by triggering primarily CCR1-mediated arrest on endothelial cells, whereas subsequent spreading is dominated by CCR5. The CCL5-induced arrest can be enhanced by heteromer formation with CXCL4. To identify mechanisms for receptor-specific functions, we employed CCL5 mutants and transfectants expressing receptor chimeras carrying transposed extracellular regions. Mutation of the basic 50s cluster of CCL5, a coordinative site for CCL5 surface presentation, reduced CCR5- but not CCR1-mediated arrest and transmigration. Impaired arrest was restored by exchanging the CCR5-N-terminus for that of CCR1, which supported arrest even without the 50s cluster, whereas mutation of the basic 40s cluster essential for proteoglycan binding of CCL5 could not be rescued. The enhancement of CCL5-induced arrest by CXCL4 was mediated by CCR1 requiring its third extracellular loop. The domain exchanges did not affect formation and co-localisation of receptor dimers, indicating a sensing role of the third extracellular loop for hetero-oligomers in an arrest microenvironment. Our data identify confined targetable regions of CCR1 specialised to facilitate CCL5-induced arrest and enhanced responsiveness to the CXCL4-CCL5 heteromer.Note: The review process for this manuscript was fully handled by G. Y. H. Lip, Editor in Chief.
Plasma Free Fatty Acids and Risk of Heart Failure
Authors: Djoussé Luc , Benkeser David , Arnold Alice , Kizer Jorge R. , Zieman Susan J. , Lemaitre Rozenn N. , Tracy Russell P. , Gottdiener John S. , Mozaffarian Dariush , Siscovick David S. , Mukamal Kenneth J. , Ix Joachim H. 
Published: August 2013

Background—
Although plasma free fatty acid (FFA) concentrations have been associated with lipotoxicity, apoptosis, and risk of diabetes mellitus and coronary heart disease, it is unclear whether FFA levels are associated with heart failure (HF).

Methods and Results—
To test the hypothesis that plasma concentration of FFAs is positively associated with incident HF, we prospectively analyzed data on 4248 men and women free of HF at baseline and >65 years old from the Cardiovascular Health Study. FFA concentration was measured in duplicate by the Wako enzymatic method. Incident HF was validated by a centralized Events Committee. We used Cox proportional hazards to estimate the hazard ratio of HF per SD of FFAs. During a median follow-up of 10.5 years, a total of 1286 new cases of HF occurred. In a multivariable model adjusting for clinic site, comorbidity, demographic, anthropometric, and lifestyle factors, each SD (0.2 mEq/L) higher plasma FFA was associated with 12% (95% confidence interval, 6%–19%) higher risk of HF. Controlling for time-varying diabetes mellitus and coronary heart disease did not change the results (hazard ratio per SD, 1.16 [95% confidence interval, 1.09–1.23]).

Conclusions—
A single measure of plasma FFA obtained later in life is associated with a higher risk of HF in older adults. Additional studies are needed to explore biological mechanisms by which FFAs may influence the risk of HF and determine whether FFAs could serve as a novel pharmacological target for HF prevention.
Value of Early Cardiovascular Magnetic Resonance for the Prediction of Adverse Arrhythmic Cardiac Events After a First Noncomplicated ST-Segment–Elevation Myocardial Infarction
Authors: Izquierdo Maite , Ruiz-Granell Ricardo , Bonanad Clara , Chaustre Fabian , Gomez Cristina , Ferrero Angel , Lopez-Lereu Pilar , Monmeneu Jose V. , Nuñez Julio , Chorro F. Javier , Bodi Vicent 
Published: August 2013

Background—
Infarct size (IS) determined by cardiac magnetic resonance (CMR) has proven an additional value, on top of left ventricular ejection fraction (LVEF), in prediction of adverse arrhythmic cardiac events (AACEs) in chronic ischemic heart disease. Its value soon after an acute ST-segment–elevation myocardial infarction remains unknown. Our aim was to determine whether early CMR can improve AACE risk prediction after acute ST-segment–elevation myocardial infarction.

Methods and Results—

Patients admitted for a first noncomplicated ST-segment–elevation myocardial infarction were prospectively followed up. A total of 440 patients were included. All of them underwent CMR 1 week after admission. CMR-derived LVEF and IS (grams per meter squared) were quantified. AACEs included postdischarge sudden death, sustained ventricular tachycardia, and ventricular fibrillation either documented on ECG or recorded via an implantable cardioverter-defibrillator. Within a median follow-up of 2 years, 11 AACEs (2.5%) were detected: 5 sudden deaths (1.1%) and 6 spontaneous ventricular tachycardia/ventricular fibrillation. In the whole group, AACEs associated with more depressed LVEF (adjusted hazard ratio [95% confidence interval], 0.90 [0.83–0.97];
P
<0.01) and larger IS (adjusted hazard ratio [95% confidence interval], 1.06 [1.01–1.12];
P
=0.01). According to the corresponding area under the receiver operating characteristic curve, LVEF ≤36% and IS ≥23.5 g/m
2
best predicted AACEs. The vast majority of AACEs (10/11) occurred in patients with simultaneous depressed LVEF ≤36% and IS ≥23.5 g/m
2
(n=39).

Conclusions—
In the era of reperfusion therapies, occurrence of AACEs in patients with an in-hospital noncomplicated first ST-segment–elevation myocardial infarction is low. In this setting, assessment of an early CMR-derived IS could be useful for further optimization of AACE risk prediction.
Elevated Remnant Cholesterol Causes Both Low-Grade Inflammation and Ischemic Heart Disease, Whereas Elevated Low-Density Lipoprotein Cholesterol Causes Ischemic Heart Disease Without Inflammation
Authors: Varbo Anette , Benn Marianne , Tybjærg-Hansen Anne , Nordestgaard Børge G. 
Published: August 2013

Background—
Elevated nonfasting remnant cholesterol and low-density lipoprotein (LDL) cholesterol are causally associated with ischemic heart disease (IHD), but whether elevated nonfasting remnant cholesterol and LDL cholesterol both cause low-grade inflammation is currently unknown.

Methods and Results—

We studied 60 608 individuals from the Copenhagen General Population Study, the Copenhagen City Heart Study, and the Copenhagen Ischemic Heart Disease study, of whom 10 668 had IHD diagnosed between 1977 and 2011. We genotyped for variants affecting levels of nonfasting remnant cholesterol, LDL cholesterol, C-reactive protein by
CRP
alleles, and C-reactive protein by
IL6R
alleles. Using a multidirectional mendelian randomization design, we investigated possible causal associations between the lipoproteins and C-reactive protein and between the lipoproteins and IHD. A 1-mmol/L(39 mg/dL) higher level of nonfasting remnant cholesterol was associated observationally with a 37% (95% confidence interval, 35–39) higher C-reactive protein level and causally with a 28% (95% confidence interval, 10–48) higher level. For LDL cholesterol, a 1-mmol/L (39-mg/dL) higher level was associated observationally with a 7% (95% confidence interval, 6–7) higher C-reactive protein level, but we found no causal association. Likewise, higher levels of C-reactive protein did not associate causally with elevated nonfasting remnant cholesterol or LDL cholesterol. Finally, the causal risk ratio for IHD for a 1-mmol/L (39-mg/dL) higher level was 3.3 (95% confidence interval, 2.1–5.2) for nonfasting remnant cholesterol and 1.8 (95% confidence interval, 1.5–2.2) for LDL cholesterol. The causal associations for remnant cholesterol were present even in those without diabetes mellitus and obesity.

Conclusions—
Elevated nonfasting remnant cholesterol is causally associated with low-grade inflammation and with IHD, whereas elevated LDL cholesterol is associated causally with IHD without inflammation.
Effectiveness of Percutaneous Coronary Intervention With Drug‐Eluting Stents Compared With Bypass Surgery in Diabetics With Multivessel Coronary Disease: Comprehensive Systematic Review and Meta‐analysis of Randomized Clinical Data
Authors: Hakeem Abdul , Garg Nadish , Bhatti Sabha , Rajpurohit Naveen , Ahmed Zubair , Uretsky Barry F. 
Published: August 2013

Background

Controversy persists regarding the optimal revascularization strategy for diabetic patients with multivessel coronary artery disease (
MVD
). Coronary artery bypass grafting (
CABG
) has been compared with percutaneous coronary intervention (
PCI
) using drug‐eluting stents (
DES
) in recent randomized controlled trials (
RCT
s).

Methods and Results

RCT
s comparing
PCI
with
DES
versus
CABG
in diabetic patients with
MVD
who met inclusion criteria were analyzed (protocol registration No.
CRD
42013003693). Primary end point (major adverse cardiac events) was a composite of death, myocardial infarction, and stroke at a mean follow‐up of 4 years. Analyses were performed for each outcome by using risk ratio (
RR
) by fixed‐ and random‐effects models. Four
RCTS
with 3052 patients met inclusion criteria (1539
PCI
versus 1513
CABG
). Incidence of major adverse cardiac events was 22.5% for
PCI
and 16.8% for
CABG
(
RR
1.34, 95%
CI
1.16 to 1.54,
P
<0.0001). Similar results were obtained for death (14% versus 9.7%,
RR
1.51, 95%
CI
1.09 to 2.10,
P
=0.01), and
MI
(10.3% versus 5.9%,
RR
1.44, 95%
CI
0.79 to 2.6,
P
=0.23). Stroke risk was significantly lower with
DES
(2.3% versus 3.8%,
RR
0.59, 95%
CI
0.39 to 0.90,
P
=0.01) and subsequent revascularization was several‐fold higher (17.4% versus 8.0%,
RR
1.85, 95%
CI
1.0 to 3.40,
P
=0.05).

Conclusions

These data demonstrate that
CABG
in diabetic patients with
MVD
at low to intermediate surgical risk (defined as EUROSCORE <5) is superior to
MVD PCI
with
DES
.
CABG
decreased overall death, nonfatal myocardial infarction, and repeat revascularization at the expense of an increase in stroke risk.
A Case Study of Patriarchy and Slavery: The Hermeneutical Importance of Qurʾānic Assumptions in the Development of a Values-Based and Purposive Oriented Qurʾān-sunna Hermeneutic
Authors: Duderija Adis 
Published: August 2013

Abstract
It is the task of this paper to argue that the development of a new Qurʾān-sunna hermeneutic (and therefore Islamic legal theory) which hermeneutically privileges an ethico-religious and purposive approach to a Qurʾānic interpretation (based on ethically objectivist nature of ethical value) has the potential to engender a gender symmetrical Islamic law. In order for this to be achieved, it is argued further, that the hermeneutical importance of the mirroring of the various socio-cultural and ethico-moral assumptions prevalent in the Qurʾān’s revelatory milieu in the actual Qurʾānic text itself must be taken into account as evident in those passages pertaining to the patriarchal nature of socio-legal aspects of gender dynamics and existence of slavery, especially female concubinage. Additionally, in the first part of the paper, I briefly discuss one reason why I consider the classical Islamic scholarship failed to explore the hermeneutical significance of these assumptions and therefore did not engender a Qurʾānic hermeneutic and Islamic legal theory that hermeneutically privileges an ethico-religious and purposive based approach to interpretation of Qurʾān and sunna. I refer to this process as a hermeneutical shift from a Qurʾān-sunna interpretive dialogical approach to that of a sunna-ḥadith episteme.
Strong Down-Valley Low-Level Jets over the Atacama Desert: Observational Characterization
Authors: Muñoz Ricardo C. , Falvey Mark J. , Araya Marcelo , Jacques-Coper Martin 
Published: August 2013

AbstractThe near-surface wind and temperature regime at three points in the Atacama Desert of northern Chile is described using two years of multilevel measurements from 80-m towers located in an altitude range between 2100 and 2700 m MSL. The data reveal the frequent development of strong nocturnal drainage flows at all sites. Down-valley, nose-shaped wind speed profiles are observed, with maximum values occurring at heights between 20 and 60 m AGL. The flow intensity shows considerable interdaily variability and a seasonal modulation of maximum speeds, which in the cold season can attain hourly average values of more than 20 m s−1. Turbulent mixing appears to be important over the full tower layer, affecting the curvature of the nighttime temperature profile and possibly explaining the observed increase of surface temperatures in the down-valley direction. Nocturnal valley winds and temperatures are weakly controlled by upper-air conditions observed at the nearest aerological station. Estimates of terms in the momentum budget for the development and quasi-stationary phases of the down-valley flows suggest that the pressure gradient force due to the near-surface cooling along the sloping valley axes plays an important role in these drainage flows. A scale for the jet nose height of equilibrium turbulent down-slope jets is proposed that is based on surface friction velocity and surface inversion intensity. At one of the sites, this scale explains about 70% of the case-to-case observed variance of jet nose heights. Further modeling and observations are needed, however, to define better the dynamics, extent, and turbulence structure of this flow system, which has significant wind-energy, climatic, and environmental implications.
The Influence of Submeso Processes on Stable Boundary Layer Similarity Relationships
Authors: Acevedo Otávio C. , Costa Felipe D. , Oliveira Pablo E. S. , Puhales Franciano S. , Degrazia Gervásio A. , Roberti Débora R. 
Published: August 2013

AbstractPrevious observational studies in the stable boundary layer diverge appreciably on the values of dimensionless ratios between turbulence-related quantities and on their stability dependence. In the present study, the hypothesis that such variability is caused by the influence of locally dependent nonturbulent processes, referred to as submeso, is tested and confirmed. This is done using six datasets collected at sites with different surface coverage. The time-scale dependence of wind components and temperature fluctuations is presented using the multiresolution decomposition, which allows the identification of the turbulence and submeso contributions to spectra and cospectra. In the submeso range, the spectra of turbulence kinetic energy range increases exponentially with time scale. The exponent decreases with the magnitude of the turbulent fluctuations at a similar manner at all sites. This fact is used to determine the smaller time scale with relevant influence of submeso processes and a ratio that quantifies the relative importance of such nonturbulent processes with respect to turbulence. Based on that, values for the local stability parameter that are unaffected by nonturbulent processes are found. It is shown that the dimensionless ratios do not usually converge to a given value as the time scale increases and that it is as a consequence of the locally dependent submeso influence. The ratios and their stability dependence are determined at the time scales with least influence of nonturbulent processes, but significant site-to-site variability persists. Combining all datasets, expressions for the dependence of the dimensionless ratios on the local stability parameter that minimize the role of the submeso contribution are proposed.