bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcription Factor NF-Y Induces Apoptosis in Cells Expressing Wild-Type p53 through E2F1 Upregulation and p53 Activation
Authors: Gurtner Aymone , Fuschi Paola , Martelli Fabio , Manni Isabella , Artuso Simona , Simonte Giacoma , Ambrosino Valeria , Antonini Annalisa , Folgiero Valentina , Falcioni Rita , Sacchi Ada , Piaggio Giulia 
Published: October 2010

Abstract
The CCAAT-binding transcription factor NF-Y plays a central role in regulating cellular proliferation by controlling the expression of genes required for cell-cycle progression such as cyclin A, cyclin B1, cyclin B2, cdc25A, cdc25C, and cdk1. Here we show that unrestricted NF-Y activity leads to apoptosis in an E2F1- and wild-type p53 (wtp53)-dependent manner. Unrestricted NF-Y activity induced an increase in E2F1 mRNA and protein levels. Furthermore, NF-Y directly bound the E2F1 promoter and this correlated with the appearance of open chromatin marks. The ability of NF-Y to induce apoptosis was impaired in cells lacking E2F1 and wtp53. Moreover, NF-Y overexpression elicited phosphorylation of wt p53Ser18 in an E2F1-dependent manner. Our findings establish that NF-Y acts upstream of E2F1 in p53-mediated apoptosis. Cancer Res; 70(23); 9711–20. ©2010 AACR.
p53 Status in Stromal Fibroblasts Modulates Tumor Growth in an SDF1-Dependent Manner
Authors: Addadi Yoseph , Moskovits Neta , Granot Dorit , Lozano Guillermina , Carmi Yaron , Apte Ron N. , Neeman Michal , Oren Moshe 
Published: October 2010

Abstract
The p53 tumor suppressor exerts a variety of cell-autonomous effects that are aimed to thwart tumor development. In addition, however, there is growing evidence for cell nonautonomous tumor suppressor effects of p53. In the present study, we investigated the impact of stromal p53 on tumor growth. Specifically, we found that ablation of p53 in fibroblasts enabled them to promote more efficiently the growth of tumors initiated by PC3 prostate cancer-derived cells. This stimulatory effect was dependent on the increased expression of the chemokine SDF-1 in the p53-deficient fibroblasts. Notably, fibroblasts harboring mutant p53 protein were more effective than p53-null fibroblasts in promoting tumor growth. The presence of either p53-null or p53-mutant fibroblasts led also to a markedly elevated rate of metastatic spread of the PC3 tumors. These findings implicate p53 in a cell nonautonomous tumor suppressor role within stromal fibroblasts, through suppressing the production of tumor stimulatory factors by these cells. Moreover, expression of mutant p53 by tumor stroma fibroblasts might exert a gain of function effect, further accelerating tumor development. Cancer Res; 70(23); 9650–8. ©2010 AACR.
Inhibition of ALK, PI3K/MEK, and HSP90 in Murine Lung Adenocarcinoma Induced by EML4-ALK Fusion Oncogene
Authors: Chen Zhao , Sasaki Takaaki , Tan Xiaohong , Carretero Julian , Shimamura Takeshi , Li Danan , Xu Chunxiao , Wang Yuchuan , Adelmant Guillaume O. , Capelletti Marzia , Lee Hyun Joo , Rodig Scott J. , Borgman Christa , Park Seung-il , Kim Hyeong Ryul , Padera Robert , Marto Jarrod A. , Gray Nathanael S. , Kung Andrew L. , Shapiro Geoffrey I. , Jänne Pasi A. , Wong Kwok-Kin 
Published: October 2010

Abstract
Genetic rearrangements of the anaplastic lymphoma kinase (ALK) kinase occur in 3% to 13% of non–small cell lung cancer patients and rarely coexist with KRASor EGFR mutations. To evaluate potential treatment strategies for lung cancers driven by an activated EML4-ALK chimeric oncogene, we generated a genetically engineered mouse model that phenocopies the human disease where this rearranged gene arises. In this model, the ALK kinase inhibitor TAE684 produced greater tumor regression and improved overall survival compared with carboplatin and paclitaxel, representing clinical standard of care. 18F-FDG-PET-CT scans revealed almost complete inhibition of tumor metabolic activity within 24 hours of TAE684 exposure. In contrast, combined inhibition of the PI3K/AKT and MEK/ERK1/2 pathways did not result in significant tumor regression. We identified EML4-ALK in complex with multiple cellular chaperones including HSP90. In support of a functional reliance, treatment with geldanamycin-based HSP90 inhibitors resulted in rapid degradation of EML4-ALK in vitro and substantial, albeit transient, tumor regression in vivo. Taken together, our findings define a murine model that offers a reliable platform for the preclinical comparison of combinatorial treatment approaches for lung cancer characterized by ALK rearrangement.Cancer Res; 70(23); 9827–36. ©2010 AACR.
Genomic Deregulation during Metastasis of Renal Cell Carcinoma Implements a Myofibroblast-Like Program of Gene Expression
Authors: López-Lago Miguel A. , Thodima Venkata J. , Guttapalli Asha , Chan Timothy , Heguy Adriana , Molina Ana M. , Reuter Victor E. , Motzer Robert J. , Chaganti Raju S. K. 
Published: October 2010

Abstract
Clear cell renal cell carcinoma (RCC) is the most common and invasive adult kidney cancer. The genetic and biological mechanisms that drive metastatic spread of RCC remain largely unknown. We have investigated the molecular signatures and underlying genomic aberrations associated with RCC metastasis, using an approach that combines a human xenograft model; expression profiling of RNA, DNA, and microRNA (miRNA); functional verification; and clinical validation. We show that increased metastatic activity is associated with acquisition of a myofibroblast-like signature in both tumor cell lines and in metastatic tumor biopsies. Our results also show that the mesenchymal trait did not provide an invasive advantage to the metastatic tumor cells. We further show that some of the constituents of the mesenchymal signature, including the expression of the well-characterized myofibroblastic marker S100A4, are functionally relevant. Epigenetic silencing and miRNA-induced expression changes accounted for the change in expression of a significant number of genes, including S100A4, in the myofibroblastic signature; however, DNA copy number variation did not affect the same set of genes. These findings provide evidence that widespread genetic and epigenetic alterations can lead directly to global deregulation of gene expression and contribute to the development or progression of RCC metastasis culminating in a highly malignant myofibroblast-like cell. Cancer Res; 70(23); 9682–92. ©2010 AACR.
Resveratrol, a Red Wine Polyphenol, Suppresses Pancreatic Cancer by Inhibiting Leukotriene A4 Hydrolase
Authors: Oi Naomi , Jeong Chul-Ho , Nadas Janos , Cho Yong-Yeon , Pugliese Angelo , Bode Ann M. , Dong Zigang 
Published: October 2010

AbstractThe anticancer effects of red wine have attracted considerable attention. Resveratrol (3,5,4′-trihydroxy-trans -stilbene) is a well-known polyphenolic compound of red wine with cancer chemopreventive activity. However, the basis for this activity is unclear. We studied leukotriene A4 hydrolase (LTA4H) as a relevant target in pancreatic cancer. LTA4H knockdown limited the formation of leukotriene B4 (LTB4), the enzymatic product of LTA4H, and suppressed anchorage-independent growth of pancreatic cancer cells. An in silico shape similarity algorithm predicted that LTA4H might be a potential target of resveratrol. In support of this idea, we found that resveratrol directly bound to LTA4H in vitro and in cells and suppressed proliferation and anchorage-independent growth of pancreatic cancer by inhibiting LTB4 production and expression of the LTB4 receptor 1 (BLT1). Notably, resveratrol exerted relatively stronger inhibitory effects than bestatin, an established inhibitor of LTA4H activity, and the inhibitory effects of resveratrol were reduced in cells where LTA4H was suppressed by shRNA-mediated knockdown. Importantly, resveratrol inhibited tumor formation in a xenograft mouse model of human pancreatic cancer by inhibiting LTA4H activity. Our findings identify LTA4H as a functionally important target for mediating the anticancer properties of resveratrol. Cancer Res; 70(23); 9755–64. ©2010 AACR.
Association of Single-Nucleotide Polymorphisms From 17 Candidate Genes With Baseline Symptom-Limited Exercise Test Duration and Decrease in Duration Over 20 Years
Authors: Sarzynski Mark A. , Rankinen Tuomo , Sternfeld Barbara , Grove Megan L. , Fornage Myriam , Jacobs David R. , Sidney Stephen , Bouchard Claude 
Published: October 2010

Background—
It is not known whether the genes involved with endurance performance during young adulthood are also involved with changes in performance. We examined the associations of gene variants with symptom-limited exercise test duration at baseline and decrease in duration over 20 years.

Methods and Results—

A total of 3783 (1835 black, 1948 white) and 2335 (1035 black, 1300 white) participants from the Coronary Artery Risk Development in Young Adults study were included in the baseline and 20-year models, respectively. Two hundred seventeen single-nucleotide polymorphisms (SNPs) in black participants and 171 in white participants from 17 genes were genotyped. In blacks, 5 SNPs in the
ATP1A2
,
HIF1A
,
NOS3
, and
PPARGC1A
loci tended to be associated (
P
<0.05) with baseline duration in a multivariate regression model. Blacks (n=99) with at least 4 of the most-favorable genotypes at these loci had an ≈2-minute longer baseline duration than those with only 2 such genotypes (
P
<0.0001). In whites, the
HIF1A
rs1957757 and
PPARGC1A
rs3774909 markers tended to be associated with baseline duration, but the association of a multimarker construct of the most-favorable genotypes at both SNPs with baseline duration was not statistically significant. In whites, 4 SNPs in the
AGT
,
AMPD1
,
ANG
, and
PPARGC1A
loci tended to be associated with decrease in exercise duration over 20 years, and those with all 4 favorable genotypes (n=40) had a 0.8-minute less decline in duration compared with those with none or 1 (n=232) (
P
<0.0001).

Conclusions—

In multimarker constructs, alleles at genes related to skeletal muscle Na
+
/K
+
transport, hypoxia, and mitochondrial metabolism are associated with symptom-limited exercise test duration over time in adults.
Metformin Use and Mortality in Ambulatory Patients With Diabetes and Heart Failure
Authors: Aguilar David , Chan Wenyaw , Bozkurt Biykem , Ramasubbu Kumudha , Deswal Anita 
Published: October 2010

Background—
Despite the common coexistence of diabetes and heart failure (HF), the optimal medial treatment of diabetes in HF patients has not been well studied. We sought to compare the association between metformin use and clinical outcomes in a cohort of ambulatory patients with diabetes and established HF.

Methods and Results—

Using propensity score–matched samples, we examined the association between metformin use and the risk of death or risk of hospitalization in a national cohort of 6185 patients with HF and diabetes treated in ambulatory clinics at Veteran Affairs medical centers. In this cohort, 1561 (25.2%) patients were treated with metformin. At 2 years of follow-up, death occurred in 246 (15.8%) patients receiving metformin and in 1177 (25.5%) patients not receiving metformin (
P
<0.001). In the propensity score–matched analysis (n=2874), death occurred in 232 (16.1%) patients receiving metformin compared with 285 (19.8%) patients not receiving metformin (hazard ratio, 0.76; 95% confidence interval, 0.63 to 0.92;
P
<0.01). In propensity score–matched analyses, HF hospitalization or total hospitalization rates were not significantly different between individuals treated with metformin compared with those not treated with metformin (hazard ratio, 0.93; 95% confidence interval, 0.74 to 1.18; and hazard ratio, 0.94; 95% confidence interval, 0.83 to 1.07, respectively).

Conclusions—
Metformin therapy was associated with lower rates of mortality in ambulatory patients with diabetes and HF. Future prospective studies are necessary to define the optimal therapy for diabetic patients with HF.
Association Between Aneurysm Shoulder Stress and Abdominal Aortic Aneurysm Expansion
Authors: Li Zhi-Yong , Sadat Umar , U-King-Im Jean , Tang Tjun Y. , Bowden David J. , Hayes Paul D. , Gillard Jonathan H. 
Published: October 2010

Background—
Aneurysm expansion rate is an important indicator of the potential risk of abdominal aortic aneurysm (AAA) rupture. Stress within the AAA wall is also thought to be a trigger for its rupture. However, the association between aneurysm wall stresses and expansion of AAA is unclear.

Methods and Results—

Forty-four patients with AAAs were included in this longitudinal follow-up study. They were assessed by serial abdominal ultrasonography and computed tomography scans if a critical size was reached or a rapid expansion occurred. Patient-specific 3-dimensional AAA geometries were reconstructed from the follow-up computed tomography images. Structural analysis was performed to calculate the wall stresses of the AAA models at both baseline and final visit. A nonlinear large-strain finite element method was used to compute the wall-stress distribution. The relationship between wall stresses and expansion rate was investigated. Slowly and rapidly expanding aneurysms had comparable baseline maximum diameters (median, 4.35 cm [interquartile range, 4.12 to 5.0 cm] versus 4.6 cm [interquartile range, 4.2 to 5.0 cm];
P
=0.32). Rapidly expanding AAAs had significantly higher shoulder stresses than slowly expanding AAAs (median, 300 kPa [interquartile range, 280 to 320 kPa] versus 225 kPa [interquartile range, 211 to 249 kPa];
P
=0.0001). A good correlation between shoulder stress at baseline and expansion rate was found (
r
=0.71;
P
=0.0001).

Conclusion—
A higher shoulder stress was found to have an association with a rapidly expanding AAA. Therefore, it may be useful for estimating the expansion of AAAs and improve risk stratification of patients with AAAs.
Hyperlipidemia-Triggered Neutrophilia Promotes Early Atherosclerosis
Authors: Drechsler Maik , Megens Remco T.A. , van Zandvoort Marc , Weber Christian , Soehnlein Oliver 
Published: October 2010

Background—

Inflammation and activation of immune cells are key mechanisms in the development of atherosclerosis. Previous data indicate important roles for monocytes and T lymphocytes in lesion formation, whereas the contribution of neutrophils remains to be firmly established. Here, we investigate the effect of hypercholesterolemia on peripheral neutrophil counts, neutrophil recruitment to atherosclerotic lesions, and the importance of neutrophils in atherosclerotic lesion formation in
Apoe
−/−
mice.

Methods and Results—
Hypercholesterolemia induces neutrophilia, which was attributable to enhanced granulopoiesis and enhanced mobilization from the bone marrow. The degree of hypercholesterolemia-induced neutrophilia was positively correlated with the extent of early atherosclerotic lesion formation. In turn, neutropenic mice display reduced plaque sizes at early but not late stages of atherosclerotic lesion formation. Flow cytometry of enzymatically digested aortas further shows altered cellular plaque composition in neutropenic mice with reduced numbers of inflammatory monocytes and macrophages. Aortic neutrophil infiltration peaks 4 weeks after the start of a high-fat diet and decreases afterward. The recruitment of neutrophils to large arteries was found to depend on CCR1, CCR2, CCR5, and CXCR2, which contrasts to peripheral venous recruitment, which requires CCR2 and CXCR2 only. The involvement of CCR1 and CCR5 corresponded to the endothelial deposition of the platelet-derived chemokine CCL5 in arteries but not in veins.

Conclusions—
Our data provide evidence that hypercholesterolemia-induced neutrophilia is multifactorial and that neutrophils infiltrate arteries primarily during early stages of atherosclerosis. Collectively, these data suggest an important role of neutrophils in the initiation of atherosclerosis.
The Horse’s Tale: Narratives of Caring for/about Horses
Authors: Hockenhull Joanna , Birke Lynda , Creighton Emma 
Published: October 2010

AbstractIn this paper, we report on a study of people who keep horses for leisure riding; the study was based on a qualitative (discourse) analysis of written comments made by people keeping horses, focusing on how they care for them and how they describe horse behavior. These commentaries followed participation in an online survey investigating management practices. The responses clustered around two significant themes: the first centered around people’s methods of caring for their animal and the dependence of such care upon external influences like human social contexts. The second theme centers on the “life stories” people constructed for their horse, usually to explain aspects of the animal’s behavior; in particular, many spoke in terms of a rescue narrative and saw their horses’ lives as being much better now than in the animal’s (imagined) previous life situation. We argue that decisions about equine well-being are made within specific social communities, which create consensus around particular ideas of what is good for horses (or other animals). To ensure the well-being of animals means taking these communities and their knowledges into account.
Horses in the South African War, c. 1899-1902
Authors: Swart Sandra 
Published: October 2010

AbstractThis essay discusses the role of horses in war through the lens of their mortality in the South African War (1899-1902). This conflict was the biggest and most modern of the numerous precolonial and colonial wars that raged across the southern African subcontinent in the late nineteenth century. Aside from the human cost, the theater of war carried a heavy environmental toll, with the scorched-earth policy shattering the rural economy. The environmental charge extended to animals. Both sides relied on mounted troops, and the casualties suffered by these animals were on a massive scale. This is widely regarded as proportionally the most devastating waste of horseflesh in military history up until that time. This paper looks at the material context of—and reasons for—equine casualties and discusses the cultural dimension of equine mortality and how combatants on both sides were affected by this intimate loss.
Zoroastrian Attitudes toward Animals
Authors: Foltz Richard 
Published: October 2010

AbstractThe ancient religion of Zoroastrianism devotes considerable attention to relations between human and nonhuman animals. All animal species are seen as being in one of two categories—either beneficent or malevolent, aligned either with the forces of good or with the forces of evil in an ongoing cosmic battle. Humans should treat each species accordingly, zealously protecting “beneficent” species while ruthlessly exterminating “malevolent” ones. Zoroastrian attitudes toward nonhuman animals have likely had a range of influences, both positive and negative, on those found in other traditions, especially Judaism, Christianity, and Islam.
The Possible Role of Companion-Animal Anthropomorphism and Social Support in the Physical and Psychological Health of Dog Guardians
Authors: Duvall Antonacopoulos Nikolina M. , Pychyl Timothy A. 
Published: October 2010

AbstractWhile previous research suggests that individuals who humanize their companion animals may have insufficient human social support (Epley, Waytz, & Cacioppo, 2007), researchers have not examined the relation between companion-animal anthropomorphism and the health of animal guardians while taking into consideration their human social support levels. It was hypothesized that dog guardians with low levels of human social support would have poorer health if they engaged in high rather than low levels of anthropomorphism, while the health of dog guardians with high levels of human social support would not vary depending on their anthropomorphism levels. A sample of 203 Canadian dog guardians completed an online survey. Results revealed that, among dog guardians with low levels of human social support, those who engaged in high levels of anthropomorphism were more depressed, visited the doctor more often, and took more medications. Furthermore, among dog guardians with high levels of human social support, those who engaged in high levels of anthropomorphism were more stressed and depressed. These findings highlight the complexity of the relationship between anthropomorphic behavior, human social support, and dog guardians’ health.
Human Uniqueness in the Age of Ape Language Research
Authors: Trachsel Mary 
Published: October 2010

AbstractThis paper summarizes the debate on human uniqueness launched by Charles Darwin’s publication of The Origin of Species in 1859. In the progress of this debate, Noam Chomsky’s introduction of the Language-Acquisition Device (LAD) in the mid-1960s marked a turn to the machine model of mind that seeks human uniqueness in uniquely human components of neural circuitry. A subsequent divergence from the machine model can be traced in the short history of ape language research (ALR). In the past fifty years, the focus of ALR has shifted from the search for behavioral evidence of syntax in the minds of individual apes to participant-observation of coregulated interactions between humans and nonhuman apes. Rejecting the computational machine model of mind, the laboratory methodologies of ALR scientists Tetsuro Matsuzawa and Sue Savage-Rumbaugh represent a worldview coherent with Darwin’s continuity hypothesis.
Critique of a Critique: Do Zoos and Aquariums Promote Attitude Change in Visitors?
Authors: Falk John H. , Heimlich Joe E. , Vernon Cynthia L. , Bronnenkant Kerry 
Published: October 2010

AbstractMarino et al. (2010) recently published a critique of a three-year National Science Foundation—funded investigation of the impact of zoo and aquarium visits on the public’s understanding of animals and their attitudes toward conservation (Falk, Heimlich, & Bronnenkant, 2008; Falk, Reinhard, Vernon, Bronnenkant, Deans, & Heimlich, 2007; Heimlich, Bronnenkant, Witgert, & Falk, 2004). This critique of that critique will show that Marino et al. seriously misrepresent both the intent of the research and the methods used. The methods used by Falk and his colleagues were consistent with current, accepted research practice and their conclusions regarding impact were congruent with a growing body of scientific research (National Research Council, 2009; Ballantyne et al., 2007) showing that visits to zoos and aquariums almost always result in enhanced scientific understanding and strengthened beliefs in the value of nature conservation.
Two Trips across One Globe: Earth and Planet Earth Fothergill, A., & Linfield, M. (Directors). (2007). Earth [Documentary]. United States: Disneynature. Fothergill, A. (Director). (2006). Planet Earth. [Television series]. United Kingdom: BBC/Greenlight Media/Discovery Channel.
Authors: Woodson Mary Beth 
Published: October 2010

AbstractThis review explores the twin documentaries Earth and Planet Earth. Both are structured with the same goal of exploring our planet and its nonhuman animal inhabitants, but they diverge in approach. Using Disney’s “True-Life Adventure” series as an ideal, the view of human-nonhuman animal relations presented in Earth differs from the one presented in Planet Earth. While the former relies strongly on a purified image that mirrors traditional (Western, human) ideals, the latter presents an image that is both less “neat” and less reliant on attributing humanlike qualities to nonhuman animals. There are some similarities, however, especially regarding the human role in the future survival of the planet’s nonhuman animals.