bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of tannins on protein, dry matter, and energy digestion in moose (Alces alces)
Authors: Spalinger D. E. , Collins W. B. , Hanley T. A. , Cassara N. E. , Carnahan A. M. 
Published: October 2010

Recent work suggests that moose ( Alces alces (L., 1758)) in the boreal ecoregion may be nutritionally limited by the availability of protein as a consequence of both low nitrogen (N) concentrations and high tannin levels in their principal foods. However, the ability of moose to digest protein in the presence of tannins is unknown. We undertook a series of digestion trials with captive moose to quantify the effects of tannins and compare the digestive capabilities of moose to other browsing cervids. We fed four moose 14 single-species diets including 10 native tannin-containing forages and 4 non-tanniferous foods over four winters. True protein digestibility in moose was 92%, and metabolic fecal N excretion was estimated at 0.389 g N/100 g dry matter (DM) intake. Tannins reduced protein digestion, on average, by 38%, and the rate of reduction in protein digestion was estimated to be 8.28 g protein/100 g DM per unit protein-precipitating capacity. The digestion of protein, neutral detergent fiber, DM, and energy of tanniferous foods was not significantly different between moose and mule ( Odocoileus hemionus (Rafinesque, 1817)) or white-tailed deer ( Odocoileus virginianus (Zimmermann, 1780)). However, our experiments provide refined assays for evaluating the nutritional quality of browses for moose.
Seasonally contrasting life-history strategies in the land snail Cornu aspersum: physiological and ecological implications
Authors: Nicolai A. , Filser J. , Briand V. , Charrier M. 
Published: October 2010

When a life history is characterized by both seasonality in reproduction and seasonality in offspring fitness, trade-offs in reproductive traits might be adjustments to seasonal time constraints to optimize reproductive success. Therefore, we compared in the laboratory the trade-offs in reproductive traits between early (after maturity) and delayed (after dormancy) reproduction in young land snails Cornu aspersum (Müller, 1774) (syn. Helix aspersa ), depending on food energy content. We also investigated the maternal investment in reproductive output in both breeding periods. After attaining maturity, snails produced single clutches with many small eggs, which resulted, in contrast to previous studies, in large offspring with a low hatching rate owing to high within-clutch cannibalism. The young cannibals may have a higher survival probability in the following hibernation. Snails starting to reproduce after hibernation had smaller clutches of larger eggs, resulting in high quantity of lighter offspring. The clutch mass was positively correlated with maternal mass in snails reproducing after having attained maturity and negatively correlated in snails reproducing after hibernation. Multiple oviposition occurred only after hibernation, thereby enhancing reproductive success. An energy-rich diet did not affect reproductive strategies. Further studies should focus on seasonal plasticity of reproductive strategies in natural populations of C. aspersum and investigate survival probabilities of breeders and juveniles in an evolutionary context.
Lack of behavioral responses of moose (Alces alces) to high ambient temperatures near the southern periphery of their range
Authors: Lowe Stacey J. , Patterson Brent R. , Schaefer James A. 
Published: October 2010

Although fundamental factors limiting geographic ranges are understood for many animal species, there is less certainty regarding how such factors influence the behavior of individuals near distributional edges. We tested the hypothesis that climate limits the southern distribution of moose ( Alces alces (L., 1758)) by documenting space use and behavior of 36 females at the margin of the species’ range in Ontario, Canada. We assessed temperature differences among habitats and related changes in seasonal habitat use and daily movement patterns in response to temperature. Ambient temperatures frequently exceeded the thresholds of –5 °C (winter) and 14 °C (summer), above which moose are supposed to be thermally stressed. We detected no differences in habitat use relative to thermoregulation thresholds. However, moose exhibited reduced movement when snow was deep and were more active at dawn and dusk. Low variability in temperature among habitat types implied that functional thermal shelters were absent. We suggest that moose in their southern range either ameliorate heat stress at a finer resolution than we measured or are more resilient to temperature than previously thought. Additional evidence linking temperatures with negative responses is necessary before the prevalent hypothesis of heat stress limiting the southern distribution of moose can be fully assessed.
Integrating streamer and ocean-bottom seismic data for sub-basalt imaging on the Atlantic Margin
Authors: Lau K. W. Helen , White R. S. , Christie P. A. F. 
Published: October 2010

ABSTRACT
Stacked basalt flows cover much of the NW European continental margin, including potentially prospective sediments of the Faroes shelf. Such flows attenuate seismic energy, hindering sub-basalt structural imaging which is critical for both exploration and tectonic studies. Low-frequency, long-offset reflection surveys have yielded improved images below top basalt, while coincident ocean-bottom seismometer (OBS) data have mapped low velocity zones (LVZ) from tomographic inversion. Image correlation in a common depth domain is challenged by low spatial resolution of the tomographic image, the absence of turning rays in a LVZ and the lack of wide-angle arrivals in the reflection data. We integrate densely sampled reflection data with deep velocities from OBS data to give a common velocity model in a new, iterated, pre-stack depth-migration workflow using complementary constraints from the two datasets. The matched velocity model and depth image enable interpretation of (i) a uniform flood basalt sequence, 2–4 km thick beneath the Fugloy Ridge, with velocities correlating with those in the Lopra 1/1A borehole and (ii) a sub-basalt LVZ with chaotic reflections corresponding to sill-intruded, probably syn-rift sediments. Such a workflow could be extended to targets beneath high velocity salt or basalt and could provide constraints for 3D datasets.

Supplementary material:
Overlays of modelled arrival times on all the OBS gathers, similar to Figure 4, can be found at
http://www.geolsoc.org.uk/SUP18433
Definition of Ubiquitination Modulator COP1 as a Novel Therapeutic Target in Human Hepatocellular Carcinoma
Authors: Lee Yun-Han , Andersen Jesper B. , Song Ho-Taek , Judge Adam D. , Seo Daekwan , Ishikawa Tsuyoshi , Marquardt Jens U. , Kitade Mitsuteru , Durkin Marian E. , Raggi Chiara , Woo Hyun Goo , Conner Elizabeth A. , Avital Itzhak , MacLachlan Ian , Factor Valentina M. , Thorgeirsson Snorri S. 
Published: October 2010

Abstract
The development of targeted therapeutics for hepatocellular carcinoma (HCC) remains a major challenge. The ubiquitination modulator COP1 regulates p53 activity by ubiquitination and it is frequently overexpressed in human HCC. In this study, we tested the hypothesis that COP1 blockade by short interfering RNA (siRNA)–mediated inhibition could affect the course of HCC progression. The COP1 isoform COP1-1 was selected as the most effective target for siRNAs in terms of growth inhibition and apoptotic induction in several HCC cell lines. Growth inhibition occurred in HCC cells that retained wild-type p53 or expressed mutant p53 (Y220C or R249S), whereas p53-null Hep3B cells were resistant. Microarray expression analysis revealed that the antiproliferative effects of COP1 blockade were driven by a common subset of molecular alterations including a p53-associated functional network. In an orthotopic mouse xenograft model of HCC, systemic delivery of a modified COP1 siRNA by stable nucleic acid–lipid particles suppressed neoplastic growth in liver without unwanted immune responses. Our findings offer a first proof of principle that COP1 can be a promising target for systemic therapy of HCC. Cancer Res; 70(21); 8264–9. ©2010 AACR.
Overexpression of Transcription Factor Sp2 Inhibits Epidermal Differentiation and Increases Susceptibility to Wound- and Carcinogen-Induced Tumorigenesis
Authors: Kim Tae-Hyung , Chiera Shannon L. , Linder Keith E. , Trempus Carol S. , Smart Robert C. , Horowitz Jonathan M. 
Published: October 2010

Abstract
Sp proteins are evolutionarily conserved transcription factors required for the expression of a wide variety of genes that are critical for development and cell cycle progression. Deregulated expression of certain Sp proteins is associated with the formation of a variety of human tumors; however, direct evidence that any given Sp protein is oncogenic has been lacking. Here, we report that Sp2 protein abundance in mice increases in concert with the progression of carcinogen-induced murine squamous cell carcinomas. Transgenic mice specifically overexpressing murine Sp2 in epidermal basal keratinocytes were highly susceptible to wound- and carcinogen-induced papillomagenesis. Transgenic animals that were homozygous rather than hemizygous for the Sp2 transgene exhibited a striking arrest in the epidermal differentiation program, perishing within 2 weeks of birth. Our results directly support the likelihood that Sp2 overexpression occurring in various human cancers has significant functional effect. Cancer Res; 70(21); 8507–16. ©2010 AACR.
Ablation of TAK1 Upregulates Reactive Oxygen Species and Selectively Kills Tumor Cells
Authors: Omori Emily , Matsumoto Kunihiro , Zhu Songyun , Smart Robert C. , Ninomiya-Tsuji Jun 
Published: October 2010

Abstract
TAK1 kinase activates multiple transcription factors and regulates the level of reactive oxygen species (ROS). We have previously reported that ablation of TAK1 in keratinocytes causes hypersensitivity to ROS-induced cell apoptosis. It is known that some tumor cells produce ROS at higher levels compared with normal cells. We used inducible epidermal-specific TAK1 knockout mice and examined whether ablation of TAK1 in preexisting skin tumors could cause an increase in ROS and result in tumor cell death. Deletion of tak1 gene in skin tumors caused the accumulation of ROS and increased apoptosis, and skin tumors totally regressed within 5 to 10 days. Normal skin did not exhibit any significant abnormality on tak1 gene deletion. Thus, TAK1 kinase could be a new and effective molecular target for ROS-based tumor killing. Cancer Res; 70(21); 8417–25. ©2010 AACR.
Tissue-Specific Pathways for Estrogen Regulation of Ovarian Cancer Growth and Metastasis
Authors: Spillman Monique A. , Manning Nicole G. , Dye Wendy W. , Sartorius Carol A. , Post Miriam D. , Harrell Joshua Chuck , Jacobsen Britta M. , Horwitz Kathryn B. 
Published: October 2010

Abstract
Menopausal estrogen (E2) replacement therapy increases the risk of estrogen receptor (ER)–positive epithelial ovarian cancers (EOC). Whether E2 is tumorigenic or promotes expansion of undiagnosed preexisting disease is unknown. To determine E2 effects on tumor promotion, we developed an intraperitoneal mouse xenograft model using ZsGreen fluorescent ER− 2008 and ER+ PEO4 human EOC cells. Tumor growth was quantified by in vivo fluorescent imaging. In ER+ tumors, E2 significantly increased size, induced progesterone receptors, and promoted lymph node metastasis, confirming that ERs are functional and foster aggressiveness. Laser-captured human EOC cells from ER− and ER+ xenografted tumors were profiled for expression of E2-regulated genes. Three classes of E2-regulated EOC genes were defined, but &lt;10% were shared with E2-regulated breast cancer genes. Because breast cancer selective ER modulators (SERM) are therapeutically ineffective in EOC, we suggest that our EOC-specific E2-regulated genes can assist pharmacologic discovery of ovarian-targeted SERM. Cancer Res; 70(21); 8927–36. ©2010 AACR.
Early Detection of Recurrent Breast Cancer Using Metabolite Profiling
Authors: Asiago Vincent M. , Alvarado Leiddy Z. , Shanaiah Narasimhamurthy , Gowda G.A. Nagana , Owusu-Sarfo Kwadwo , Ballas Robert A. , Raftery Daniel 
Published: October 2010

Abstract
We report on the development of a monitoring test for recurrent breast cancer, using metabolite-profiling methods. Using a combination of nuclear magnetic resonance (NMR) and two-dimensional gas chromatography–mass spectrometry (GC×GC-MS) methods, we analyzed the metabolite profiles of 257 retrospective serial serum samples from 56 previously diagnosed and surgically treated breast cancer patients. One hundred sixteen of the serial samples were from 20 patients with recurrent breast cancer, and 141 samples were from 36 patients with no clinical evidence of the disease during ∼6 years of sample collection. NMR and GC×GC-MS data were analyzed by multivariate statistical methods to compare identified metabolite signals between the recurrence samples and those with no evidence of disease. Eleven metabolite markers (seven from NMR and four from GC×GC-MS) were shortlisted from an analysis of all patient samples by using logistic regression and 5-fold cross-validation. A partial least squares discriminant analysis model built using these markers with leave-one-out cross-validation provided a sensitivity of 86% and a specificity of 84% (area under the receiver operating characteristic curve = 0.88). Strikingly, 55% of the patients could be correctly predicted to have recurrence 13 months (on average) before the recurrence was clinically diagnosed, representing a large improvement over the current breast cancer–monitoring assay CA 27.29. To the best of our knowledge, this is the first study to develop and prevalidate a prediction model for early detection of recurrent breast cancer based on metabolic profiles. In particular, the combination of two advanced analytical methods, NMR and MS, provides a powerful approach for the early detection of recurrent breast cancer. Cancer Res; 70(21); 8309–18. ©2010 AACR.
Cediranib/AZD2171 Inhibits Bone and Brain Metastasis in a Preclinical Model of Advanced Prostate Cancer
Authors: Yin Juan Juan , Zhang Luhua , Munasinghe Jeeva , Linnoila R. Ilona , Kelly Kathleen 
Published: October 2010

Abstract
Late stage or aggressive cancers exhibit metastatic growth at multiple sites, and the characterization of treatment response in various organs to drugs with potentially wide-ranging efficacy is needed. Tumor cells that induce angiogenesis are a common characteristic of metastatic disease, and clinically, antiangiogenic therapies have shown value in the setting of advanced cancer. However, recent preclinical studies have suggested that exposure to antiangiogenic drugs can increase tumor invasiveness and metastasis, making it important to determine which contexts antiangiogenic therapy is most appropriate. We describe here the effects of cediranib, a receptor tyrosine kinase inhibitor, in a model of advanced prostate cancer metastatic to skeleton and brain. Treatment with cediranib decreased metastatic tumor burden in the brain and bone, decreased cerebral vasogenic edema, and improved survival, despite increasing the invasive histology of brain metastases. Short-duration cediranib treatment given at the time of tumor cell dissemination was sufficient to inhibit the establishment and subsequent growth of bone metastases, although brain metastases were subject to rebound growth after the discontinuation of cediranib. Distinct growth patterns at different organ sites in the same animal showed that certain tumor microenvironments such as bone may be most amenable to interventions by anti–vascular endothelial growth factor (VEGF) therapies. In addition, anti-VEGF treatment may be of utility in decreasing the rapid growth of solid brain metastases and vasogenic edema in patients with advanced cancer, leading to reduced morbidity and associated clinical benefit. Cancer Res; 70(21); 8662–73. ©2010 AACR.
K-ras Mutation Targeted to Gastric Tissue Progenitor Cells Results in Chronic Inflammation, an Altered Microenvironment, and Progression to Intraepithelial Neoplasia
Authors: Okumura Tomoyuki , Ericksen Russell E. , Takaishi Shigeo , Wang Sophie S.W. , Dubeykovskiy Zinaida , Shibata Wataru , Betz Kelly S. , Muthupalani Sureshkuma , Rogers Arlin B. , Fox James G. , Rustgi Anil K. , Wang Timothy C. 
Published: October 2010

Abstract
Chronic infectious diseases, such as Helicobacter pylori infection, can promote cancer in a large part through induction of chronic inflammation. Oncogenic K-ras mutation in epithelial cells activates inflammatory pathways, which could compensate for a lack of infectious stimulus. Gastric histopathology and putative progenitor markers [doublecortin and calcium/calmodulin-dependent protein kinase-like 1 (Dcamkl1) and keratin 19 (K19)] in K19-K-ras-V12 (K19-kras) transgenic mice were assessed at 3, 6, 12, and 18 months of age, in comparison with Helicobacter felis–infected wild-type littermates. Inflammation was evaluated by reverse transcription–PCR of proinflammatory cytokines, and K19-kras mice were transplanted with green fluorescent protein (GFP)–labeled bone marrow. Both H. felis infection and K-ras mutation induced upregulation of proinflammatory cytokines, expansion of Dcamkl1+ cells, and progression to oxyntic atrophy, metaplasia, hyperplasia, and high-grade dysplasia. K19-kras transgenic mice uniquely displayed mucous metaplasia as early as 3 months and progressed to high-grade dysplasia and invasive intramucosal carcinoma by 20 months. In bone marrow–transplanted K19-kras mice that progressed to dysplasia, a large proportion of stromal cells were GFP+ and bone marrow–derived, but only rare GFP+ epithelial cells were observed. GFP+ bone marrow–derived cells included leukocytes and CD45− stromal cells that expressed vimentin or α smooth muscle actin and were often found surrounding clusters of Dcamkl1+ cells at the base of gastric glands. In conclusion, the expression of mutant K-ras in K19+ gastric epithelial cells can induce chronic inflammation and promote the development of dysplasia. Cancer Res; 70(21); 8435–45. ©2010 AACR.
Detection of Elevated Plasma Levels of Epidermal Growth Factor Receptor Before Breast Cancer Diagnosis among Hormone Therapy Users
Authors: Pitteri Sharon J. , Amon Lynn M. , Busald Buson Tina , Zhang Yuzheng , Johnson Melissa M. , Chin Alice , Kennedy Jacob , Wong Chee-Hong , Zhang Qing , Wang Hong , Lampe Paul D. , Prentice Ross L. , McIntosh Martin W. , Hanash Samir M. , Li Christopher I. 
Published: October 2010

Abstract
Applying advanced proteomic technologies to prospectively collected specimens from large studies is one means of identifying preclinical changes in plasma proteins that are potentially relevant to the early detection of diseases such as breast cancer. We conducted 14 independent quantitative proteomics experiments comparing pooled plasma samples collected from 420 estrogen receptor–positive (ER+) breast cancer patients ≤17 months before their diagnosis and matched controls. Based on the more than 3.4 million tandem mass spectra collected in the discovery set, 503 proteins were quantified, of which 57 differentiated cases from controls with a P value of &lt;0.1. Seven of these proteins, for which quantitative ELISA assays were available, were assessed in an independent validation set. Of these candidates, epidermal growth factor receptor (EGFR) was validated as a predictor of breast cancer risk in an independent set of preclinical plasma samples for women overall [odds ratio (OR), 1.44; P = 0.0008] and particularly for current users of estrogen plus progestin (E + P) menopausal hormone therapy (OR, 2.49; P = 0.0001). Among current E + P users, the EGFR sensitivity for breast cancer risk was 31% with 90% specificity. Whereas the sensitivity and specificity of EGFR are insufficient for a clinically useful early detection biomarker, this study suggests that proteins that are elevated preclinically in women who go on to develop breast cancer can be discovered and validated using current proteomic technologies. Further studies are warranted to examine the role of EGFR and to discover and validate other proteins that could potentially be used for early detection of breast cancer. Cancer Res; 70(21); 8598–606. ©2010 AACR.
F3-Targeted Cisplatin-Hydrogel Nanoparticles as an Effective Therapeutic That Targets Both Murine and Human Ovarian Tumor Endothelial Cells In vivo
Authors: Winer Ira , Wang Shouyan , Lee Youg-Eun Koo , Fan Wenzhe , Gong Yusong , Burgos-Ojeda Daniela , Spahlinger Greg , Kopelman R. , Buckanovich Ronald J. 
Published: October 2010

Abstract
Recent studies indicate that ovarian cancer may be highly responsive to antivascular therapeutics. We have developed an antivascular tumor therapeutic using the F3 peptide to target cisplatin-loaded nanoparticles (F3-Cis-Np) to tumor vessels. We show that although F3-Cis-Np bind with high specificity to both human ovarian tumor cells and tumor endothelial cells in vitro, they only show cytotoxic activity against the tumor endothelial cells. In vivo these nanoparticles bind primarily to tumor endothelial cells. Therapeutic studies in both flank and orthotopic i.p. murine ovarian tumor models, as well as human tumor xenograft models, show rapid tumor regression with treatment. Treatment was associated with significant vascular necrosis consistent with an antivascular effect. Furthermore, treatment was active in both platinum-sensitive and platinum-resistant cell lines. Importantly, we show that F3-Cis-Np bind to human tumor endothelial cells in vitro and to human tumor vessels in vivo. Therapy targeting human vasculature in vivo with F3-Cis-Np led to near complete loss of all human tumor vessels in a murine model of human tumor vasculature. Our studies indicate that F3-targeted vascular therapeutics may be an effective treatment modality in human ovarian cancer. Cancer Res; 70(21); 8674–83. ©2010 AACR.
Antibodies to Merkel Cell Polyomavirus T Antigen Oncoproteins Reflect Tumor Burden in Merkel Cell Carcinoma Patients
Authors: Paulson Kelly G. , Carter Joseph J. , Johnson Lisa G. , Cahill Kevin W. , Iyer Jayasri G. , Schrama David , Becker Juergen C. , Madeleine Margaret M. , Nghiem Paul , Galloway Denise A. 
Published: October 2010

AbstractMerkel cell polyomavirus (MCPyV) is a common infectious agent that is likely involved in the etiology of most Merkel cell carcinomas (MCC). Serum antibodies recognizing the MCPyV capsid protein VP1 are detectable at high titer in nearly all MCC patients and remain stable over time. Although antibodies to the viral capsid indicate prior MCPyV infection, they provide limited clinical insight into MCC because they are also detected in more than half of the general population. We investigated whether antibodies recognizing MCPyV large and small tumor-associated antigens (T-Ag) would be more specifically associated with MCC. Among 530 population control subjects, these antibodies were present in only 0.9% and were of low titer. In contrast, among 205 MCC cases, 40.5% had serum IgG antibodies that recognize a portion of T-Ag shared between small and large T-Ags. Among cases, titers of T-Ag antibodies fell rapidly (∼8-fold per year) in patients whose cancer did not recur, whereas they rose rapidly in those with progressive disease. Importantly, in several patients who developed metastases, the rise in T-Ag titer preceded clinical detection of disease spread. These results suggest that antibodies recognizing T-Ag are relatively specifically associated with MCC, do not effectively protect against disease progression, and may serve as a clinically useful indicator of disease status. Cancer Res; 70(21); 8388–97. ©2010 AACR.