bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human Rhomboid Family-1 Suppresses Oxygen-Independent Degradation of Hypoxia-Inducible Factor-1α in Breast Cancer
Authors: Zhou Zhuan , Liu Fangfang , Zhang Zhi-Song , Shu Feifei , Zheng Yangyang , Fu Li , Li Lu-Yuan 
Published: March 2014

Abstract
Intermittent oxygen deficiency in cancers promotes prolonged inflammation, continuous angiogenesis, and increased drug resistance. Hypoxia-inducible factor-1 (HIF1) has a pivotal role in the regulation of cellular responses to oxygen deficiency. The α-subunit of HIF1 (HIF1α) is degraded in normoxia but stabilized in hypoxia. However, the molecular mechanism that controls oxygen-independent degradation of HIF1α has remained elusive. Human rhomboid family-1 (RHBDF1) is a member of a large family of nonprotease rhomboids whose function is basically unknown. We report here that RHBDF1 expression in breast cancer is highly elevated and is strongly correlated with escalated disease progression, metastasis, poor prognosis, and poor response to chemotherapy. We show that RHBDF1 interaction with the receptor of activated protein-C kinase-1 (RACK1) in breast cancer cells prevents RACK1-assisted, oxygen-independent HIF1α degradation. In addition, we show that the HIF1α-stabilizing activity of RHBDF1 diminishes when the phosphorylation of a tyrosine residue on the RHBDF1 molecule is inhibited. These findings are consistent with the view that RHBDF1 is a critical component of a molecular switch that regulates HIF1α stability in cancer cells in hypoxia and that RHBDF1 is of potential value as a new target for cancer treatment. Cancer Res; 74(10); 2719–30. ©2014 AACR.
Global Gene Repression by the Steroid Receptor Coactivator SRC-1 Promotes Oncogenesis
Authors: Walsh Claire A. , Bolger Jarlath C. , Byrne Christopher , Cocchiglia Sinead , Hao Yuan , Fagan Ailis , Qin Li , Cahalin Aoife , McCartan Damian , McIlroy Marie , O'Gaora Peadar , Xu Jianming , Hill Arnold D. , Young Leonie S. 
Published: March 2014

Abstract
Transcriptional control is the major determinant of cell fate. The steroid receptor coactivator (SRC)-1 enhances the activity of the estrogen receptor in breast cancer cells, where it confers cell survival benefits. Here, we report that a global analysis of SRC-1 target genes suggested that SRC-1 also mediates transcriptional repression in breast cancer cells. Combined SRC-1 and HOXC11 ChIPseq analysis identified the differentiation marker, CD24, and the apoptotic protein, PAWR, as direct SRC-1/HOXC11 suppression targets. Reduced expression of both CD24 and PAWR was associated with disease progression in patients with breast cancer, and their expression was suppressed in metastatic tissues. Investigations in endocrine-resistant breast cancer cell lines and SRC-1−/−/PyMT mice confirmed a role for SRC-1 and HOXC11 in downregulation of CD24 and PAWR. Through bioinformatic analysis and liquid chromatography/mass spectrometry, we identified AP1 proteins and Jumonji domain containing 2C (JMD2C/KDM4C), respectively, as members of the SRC-1 interactome responsible for transcriptional repression. Our findings deepen the understanding of how SRC-1 controls transcription in breast cancers. Cancer Res; 74(9); 2533–44. ©2014 AACR.
Comparative Functional Analysis of DPYD Variants of Potential Clinical Relevance to Dihydropyrimidine Dehydrogenase Activity
Authors: Offer Steven M. , Fossum Croix C. , Wegner Natalie J. , Stuflesser Alexander J. , Butterfield Gabriel L. , Diasio Robert B. 
Published: March 2014

Abstract
Dihydropyrimidine dehydrogenase (DPD) is the initial and rate-limiting enzyme of the uracil catabolic pathway, being critically important for inactivation of the commonly prescribed anti-cancer drug 5-fluorouracil (5-FU). DPD impairment leads to increased exposure to 5-FU and, in turn, increased anabolism of 5-FU to cytotoxic nucleotides, resulting in more severe clinical adverse effects. Numerous variants within the gene coding for DPD, DPYD, have been described, although only a few have been demonstrated to reduce DPD enzyme activity. To identify DPYD variants that alter enzyme function, we expressed 80 protein-coding variants in an isogenic mammalian system and measured their capacities to convert 5-FU to dihydro-fluorouracil, the product of DPD catabolism. The M166V, E828K, K861R, and P1023T variants exhibited significantly higher enzyme activity than wild-type DPD (120%, P = 0.025; 116%, P = 0.049; 130%, P = 0.0077; 138%, P = 0.048, respectively). Consistent with clinical association studies of 5-FU toxicity, the D949V substitution reduced enzyme activity by 41% (P = 0.0031). Enzyme activity was also significantly reduced for 30 additional variants, 19 of which had &lt;25% activity. None of those 30 variants have been previously reported to associate with 5-FU toxicity in clinical association studies, which have been conducted primarily in populations of European ancestry. Using publicly available genotype databases, we confirmed the rarity of these variants in European populations but showed that they are detected at appreciable frequencies in other populations. These data strongly suggest that testing for the reported deficient DPYD variations could dramatically improve predictive genetic tests for 5-FU sensitivity, especially in individuals of non-European descent. Cancer Res; 74(9); 2545–54. ©2014 AACR.
Fibrosis Marker Syndecan-1 and Outcome in Patients With Heart Failure With Reduced and Preserved Ejection Fraction
Authors: Tromp Jasper , van der Pol Atze , Klip IJsbrand T. , de Boer Rudolf A. , Jaarsma Tiny , van Gilst Wiek H. , Voors Adriaan A. , van Veldhuisen Dirk J. , van der Meer Peter 
Published: March 2014

Background—
Syndecan-1 is a member of the proteoglycan family involved in cell–matrix interactions. Experimental studies showed that syndecan-1 is associated with inflammation in acute myocardial infarction and remodeling. The goal of this study was to explore the role of syndecan-1 in human heart failure (HF).

Methods and Results—

We analyzed plasma syndecan-1 levels in 567 patients with chronic HF. Primary end point was a composite of all-cause mortality and rehospitalization for HF at 18 months. Mean age was 71.0±11.0 years, 38% was women, and mean left ventricular ejection fraction was 32.5±14.0%. Median syndecan-1 levels were 20.1 ng/mL (interquartile range, 13.9–27.7 ng/mL). Patients with higher syndecan-1 levels were more often men, had higher N-terminal probrain-type natriuretic peptide levels, and worse renal function. Multivariable regression analyses showed a positive correlation between syndecan-1 levels and markers of fibrosis and remodeling but no correlation with inflammation markers. Interaction analysis revealed an interaction between left ventricular ejection fraction and syndecan-1 (
P
=0.047). A doubling of syndecan-1 was associated with an increased risk of the primary outcome in patients with HF with preserved ejection fraction (hazard ratio, 2.10; 95% confidence interval, 1.14–3.86;
P
=0.017) but not in patients with HF with reduced ejection fraction (hazard ratio, 0.95; 95% confidence interval, 0.71–1.27;
P
=0.729). Finally, syndecan-1 enhanced risk classification in patients with HF with preserved ejection fraction when added to a prediction model with established risk factors.

Conclusions—
In patients with HF, syndecan-1 levels correlate with fibrosis biomarkers pointing toward a role in cardiac remodeling. Syndecan-1 was associated with clinical outcome in patients with HF with preserved ejection fraction but not in patients with HF with reduced ejection fraction.
Incremental Prognostic Value of Myocardial Fibrosis in Patients With Non–Ischemic Cardiomyopathy Without Congestive Heart Failure
Authors: Masci Pier Giorgio , Doulaptsis Constantinos , Bertella Erika , Del Torto Alberico , Symons Rolf , Pontone Gianluca , Barison Andrea , Droogné Walter , Andreini Daniele , Lorenzoni Valentina , Gripari Paola , Mushtaq Saima , Emdin Michele , Bogaert Jan , Lombardi Massimo 
Published: March 2014

Background—
We conducted a prospective longitudinal study to investigate the yet unknown clinical significance of myocardial fibrosis in patients with non–ischemic cardiomyopathy without history of congestive heart failure (CHF).

Methods and Results—

At 3 tertiary referral centers, 228 patients with non–ischemic cardiomyopathy without history of CHF were studied with cardiovascular magnetic resonance for late gadolinium enhancement (LGE) detection and quantification and prospectively followed up for a median of 23 months. The end point was a composite of cardiac death, onset of CHF, and aborted sudden cardiac death. LGE was detected in 61 (27%) patients. Thirty-one of 61 (51%) patients with LGE reached combined end point when compared with 18 of 167 (11%) patients without LGE (hazard ratio, 5.10 [2.78–9.36];
P
<0.001). Patients with LGE had greater risk of developing CHF than patients without LGE (hazard ratio, 5.23 [2.61–10.50];
P
<0.001) and higher rate of aborted sudden cardiac death (hazard ratio, 8.31 [1.66–41.55];
P
=0.010). Multivariate analysis showed that LGE was associated with high likelihood of composite end point independent of other prognostic determinants, including age; duration of cardiomyopathy; and left ventricular volumes, mass, and ejection fraction (hazard ratio, 4.02 [2.08–7.76];
P
<0.001). Improvement χ
2
analysis disclosed that LGE addition to models, including clinical data alone or in combination with parameters of left ventricular remodeling and function, yielded an improvement in outcome prediction (
P
<0.001). Addition of LGE to age and left ventricular ejection fraction improved risk stratification for composite end point (net reclassification improvement, 29.6%) and onset of CHF (net reclassification improvement, 25.4%; both
P
<0.001).

Conclusions—
In patients with non–ischemic cardiomyopathy without history of CHF, myocardial fibrosis is a strong and independent predictor of outcome, providing incremental prognostic information and improvement in risk stratification beyond clinical data and degree of left ventricular dysfunction.
Neural Substrates of the Development of Cognitive Control in Children Ages 5–10 Years
Authors: Sheridan Margaret , Kharitonova Maria , Martin Rebecca E. , Chatterjee Aparna , Gabrieli John D. E. 
Published: March 2014

Abstract
Cognitive conflict detection and resolution develops with age across childhood and likely supports age-related increases in other aspects of cognitive and emotional development. Little is known about the neural correlates of conflict detection and resolution in early childhood. In the current study, we investigated age-related change in neural recruitment during a blocked spatial-incompatibility task (Simon task) in children ages 5–10 years using fMRI. Cortical thickness was measured using structural MRI. Across all children, there was greater activation in right prefrontal and bilateral parietal cortices for incompatible than compatible conditions. In older children, compared with younger children, there was decreased activation and decreased gray matter thickness in the medial PFC. Thickness and activation changes across age were associated within participants, such that thinner cortex was associated with less activation in the rostral ACC. These findings suggest that developmental change in medial PFC activation supports performance on cognitive control tasks in early childhood.
On the Relationship Between Method and the Object of Study When Studying Religion
Authors: Warner Cameron David 
Published: March 2014

AbstractIf a discipline is defined by the object of its study, then the definition of the object of study has a priori paramount importance. Studies of the evolution of the study of religion show that researchers have been unable to escape their own socio-political contexts. I begin with a brief consideration of the evolution of superstition as a means to gain perspective on the evolution of the study of religion and definitions of religion and as a cautionary note to both the contextual study of religion and the cognitive-evolutionary (ce) study of religion. I then continue with an overview of our conference, “Researching Religion: Methodological Debates in Anthropology and the Study of Religion,” at Aarhus University, and the seven articles published in this special double issue ofNumen. Taken together, they reflect and address an international rupture between the contextual and thecestudy of religion, and point towards productive avenues for future research.
Ethics as Piety
Authors: Keane Webb 
Published: March 2014

AbstractThis article is meant as a contribution to a larger project about the relations between religion and ethics. It sketches out some approaches to the following questions: assuming that what we call “religion” and “ethics” are in principle distinct from each other, what is the conceptual relationship between them? What are the historical pathways along which the two often seem to converge? What are the social implications of that convergence where it occurs? And when they converge, what remainder escapes the conflation of these two? As a way of opening up these questions, this article compares two recent studies from the anthropology of religion, Joel Robbins’ ethnography of new evangelical Christians in Melanesia, and Charles Hirschkind’s study of a Muslim piety movement in Cairo. The comparison centers on how monotheistic religious traditions tend to objectify ethics in ways that render them cognitively explicit and thus expose them to pressures toward rationalization, generalization, and abstraction. But these traditions also expect ethics to guide everyday life, in all its concrete particularity, with potentially paradoxical consequences. These paradoxes seem to be one source of the restless urgency of those revival movements that identify ethics with piety.
Bellah’s Religion in Human Evolution: A Post-Review
Authors: Stausberg Michael 
Published: March 2014

Abstract
This essay is a “post-review,” that is, it surveys some forty book notes, reviews, and comments on Robert Bellah’s Religion in Human Evolution (2011). Because of its unusual breadth in scope the book has received praise as a magnum opus. Main issues of critical contention include the work’s minimal engagement with other evolutionary approaches in the study of religion\s, the relevance of its evolutionary perspective for the chapters on the Axial Age, and the concept of the Axial Age.
Parental Disputes, Religious Upbringing and Welfare in English Law and the ECHR
Authors: Langlaude Sylvie 
Published: March 2014

Abstract
This article assesses the position of English law concerning parental disputes about the religious upbringing of children. Despite the strong emphasis on both parents being able to direct their child’s religious upbringing, courts have interpreted the child’s welfare to restrict the exposure of the child to parental religious beliefs or practices in some circumstances: preserving the child’s future choice of religion, the physical integrity of the child, the child’s contact and relationship with both parents, the child’s educational choices, and the child’s relationship with both parents’ religious community. It is suggested that courts should have a wide understanding of welfare and should be wary to prohibit parents teaching their minority beliefs. This article also compares the position of the European Court of Human Rights (ECtHR) and suggests that, despite the stronger emphasis by the ECtHR on parental rights, English law is generally not that much at odds with the ECtHR.
On Guard at BAMlag: Representations of Guards in the 1930s Gulag Press
Authors: Thomas Alun 
Published: March 2014

The 1930s saw a dramatic escalation in the size and scope of the Soviet Union’s system of penal labour camps, the Gulag. Through analyses of memoir and other sources, the experiences of the Gulag’s prisoners at this time have been the subject of a great deal of scholarly investigation. Yet the guards who watched over these prisoners have received considerably less attention.
Newspapers printed for the VOKhR guards in the mid-1930s offer some information on their readers’ everyday duties and their status, both inside the Gulag and as citizens of the USSR. Publications taken from one particularly large camp responsible for the construction of the Baikal-Amur railway (BAMlag) depict guards as self-disciplined, industrious soldiers engaged in a war for economic and social development. But the specific dynamics and changing circumstances of the Soviet penal system at this time created an unusual contrast between newspapers printed for the guards and those printed for the prisoners of BAMlag. While the criticism levelled at prisoners by their own newspaper was often mitigated by a rehabilitative discourse, the guards were judged as full members of Soviet society, often harshly. However, the precise implications of this were rendered ambiguous by the indeterminate position of the Gulag itself at this point in Soviet history.
Hugo Zapałowicz’s species of Iris and Gladiolus (Iridaceae): Typification of his names
Authors: Zhygalova Svitlana Leonidovna , Olshanskyi Igor Grygorovych 
Published: March 2014

Iridaceae Jussieu (1789: 57) includes more than 60 genera and about 800 species (Goldblatt & Manning 2008) widely distributed in tropical, subtropical, and temperate regions, and especially numerous in Africa south of the Sahara, the eastern Mediterranean, western and eastern Asia, and Central and South America (Takhtajan 2009). Ten genera and about 100 species occur in Europe, some of which were described from Europe. We have reviewed the Herbarium of the Władysław Szafer Institute of Botany PAS (KRAM). Consequently, we here lectotypify two Iridaceae taxa described by H. Zapałowicz.
Atmospheric Tides in the Latest Generation of Climate Models*
Authors: Covey Curt , Dai Aiguo , Lindzen Richard S. , Marsh Daniel R. 
Published: March 2014

Abstract
For atmospheric tides driven by solar heating, the database of climate model output used in the most recent assessment report of the Intergovernmental Panel on Climate Change (IPCC) confirms and extends the authors’ earlier results based on the previous generation of models. Both the present study and the earlier one examine the surface pressure signature of the tides, but the new database removes a shortcoming of the earlier study in which model simulations were not strictly comparable to observations. The present study confirms an approximate consistency among observations and all model simulations, despite variation of model tops from 31 to 144 km. On its face, this result is surprising because the dominant (semidiurnal) component of the tides is forced mostly by ozone heating around 30–70-km altitude. Classical linear tide calculations and occasional numerical experimentation have long suggested that models with low tops achieve some consistency with observations by means of compensating errors, with wave reflection from the model top making up for reduced ozone forcing. Future work with the new database may confirm this hypothesis by additional classical calculations and analyses of the ozone heating profiles and wave reflection in Coupled Model Intercomparison Project (CMIP) models. The new generation of models also extends CMIP's purview to free-atmosphere fields including the middle atmosphere and above.
ENSO Asymmetry in CMIP5 Models
Authors: Zhang Tao , Sun De-Zheng 
Published: March 2014

Abstract
The El Niño–La Niña asymmetry is evaluated in 14 coupled models from phase 5 of the Coupled Model Intercomparison Project (CMIP5). The results show that an underestimate of ENSO asymmetry, a common problem noted in CMIP3 models, remains a common problem in CMIP5 coupled models. The weaker ENSO asymmetry in the models primarily results from a weaker SST warm anomaly over the eastern Pacific and a westward shift of the center of the anomaly. In contrast, SST anomalies for the La Niña phase are close to observations.
Corresponding Atmospheric Model Intercomparison Project (AMIP) runs are analyzed to understand the causes of the underestimate of ENSO asymmetry in coupled models. The analysis reveals that during the warm phase, precipitation anomalies are weaker over the eastern Pacific, and westerly wind anomalies are confined more to the west in most models. The time-mean zonal winds are stronger over the equatorial central and eastern Pacific for most models. Wind-forced ocean GCM experiments suggest that the stronger time-mean zonal winds and weaker asymmetry in the interannual anomalies of the zonal winds in AMIP models can both be a contributing factor to a weaker ENSO asymmetry in the corresponding coupled models, but the former appears to be a more fundamental factor, possibly through its impact on the mean state. The study suggests that the underestimate of ENSO asymmetry in the CMIP5 coupled models is at least in part of atmospheric origin.
On the Transfer Function between Surface Fields and the Geostrophic Stream Function in the Mediterranean Sea
Authors: Isern-Fontanet Jordi , Shinde Mahesh , González-Haro Cristina 
Published: March 2014

Abstract
The real transfer function and the phase shift between sea surface height (SSH) and sea surface buoyancy (SSB) were estimated from the output of a realistic eddy-resolving model of the Mediterranean Sea circulation. The analysis of their temporal evolution unveiled the existence of a clear seasonal cycle closely related to that of the mixed layer depth. The phase shifts between SSH and SSB attain their minimum for deep mixed layers, which is different from zero. Besides, the spectral slope of the transfer function at scales shorter than 100 km fluctuates between k−1 and k−2. For deep mixed layers, it is close to k−1, as predicted by the surface quasigeostrophic (SQG) solution. At longer wavelengths, it is approximately constant under the different environmental conditions in all of the subbasins analyzed with the exception of the Gulf of Lions. The capability to observe sea surface temperature (SST) from satellites motivated the extension of this analysis to SST and SSH. Results showed a similar qualitative behavior but with larger phase shifts. In spite of the presence of a phase shift, even for deep mixed layers, results revealed that it is still possible to reconstruct surface dynamics from SST using a transfer function, provided that the mixed layer is deep enough. For the present study, a threshold value of 70 m was enough to identify the appropriate environmental conditions. In addition, the results revealed that a precise estimation of the transfer function significantly improves the reconstruction of the flow in comparison with the application of the classical SQG solution.
Annual Cycle in Southern Tropical Indian Ocean Bottom Pressure
Authors: Piecuch Christopher G. , Ponte Rui M. 
Published: March 2014

Abstract
The seasonal monsoon drives a dynamic response in the southern tropical Indian Ocean, previously observed in baroclinic Rossby wave signatures in annual sea level and thermocline depth anomalies. In this paper, monthly mass grids based on Release-05 Gravity Recovery and Climate Experiment (GRACE) data are used to study the annual cycle in southern tropical Indian Ocean bottom pressure. To interpret the satellite data, a linear model of the ocean’s response to wind forcing—based on the theory of vertical normal modes and comprising baroclinic and barotropic components—is considered. The model is evaluated using stratification from an ocean atlas and winds from an atmospheric reanalysis. Good correspondence between model and data is found over the southern tropical Indian Ocean: the model explains 81% of the annual variance in the data on average between 10° and 25°S. Model solutions suggest that, while the annual baroclinic Rossby wave has a seafloor signature, the annual cycle in the deep sea generally involves important barotropic dynamics, in contrast to the response in the upper ocean, which is largely baroclinic.