bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association Study of Prostate Cancer Susceptibility Variants with Risks of Invasive Ovarian, Breast, and Colorectal Cancer
Authors: Song Honglin , Koessler Thibaud , Ahmed Shahana , Ramus Susan J. , Kjaer Susanne Krüger , DiCioccio Richard A. , Wozniak Eva , Hogdall Estrid , Whittemore Alice S. , McGuire Valerie , Ponder Bruce A.J. , Turnbull Clare , Hines Sarah , Rahman Nazneen ,   The Breast Cancer Susceptibility Collaboration (UK), Eeles Rosalind A. , Easton Douglas F. , Gayther Simon A. , Dunning Alison M. , Pharoah Paul D.P. 
Published: October 2008

Abstract
Several prostate cancer susceptibility loci have recently been identified by genome-wide association studies. These loci are candidates for susceptibility to other epithelial cancers. The aim of this study was to test these tag single nucleotide polymorphisms (SNP) for association with invasive ovarian, colorectal, and breast cancer. Twelve prostate cancer–associated tag SNPs were genotyped in ovarian (2,087 cases/3,491 controls), colorectal (2,148 cases/2,265 controls) and breast (first set, 4,339 cases/4,552 controls; second set, 3,800 cases/3,995 controls) case-control studies. The primary test of association was a comparison of genotype frequencies between cases and controls, and a test for trend stratified by study where appropriate. Genotype-specific odds ratios (OR) were estimated by logistic regression. SNP rs2660753 (chromosome 3p12) showed evidence of association with ovarian cancer [per minor allele OR, 1.19; 95% confidence interval (95% CI), 1.04–1.37; Ptrend = 0.012]. This association was stronger for the serous histologic subtype (OR, 1.29; 95% CI, 1.09–1.53; P = 0.003). SNP rs7931342 (chromosome 11q13) showed some evidence of association with breast cancer (per minor allele OR, 0.95; 95% CI, 0.91–0.99; Ptrend = 0.028). This association was somewhat stronger for estrogen receptor–positive tumors (OR, 0.92; 95% CI, 0.87–0.98; P = 0.011). None of these tag SNPs were associated with risk of colorectal cancer. In conclusion, loci associated with risk of prostate cancer may also be associated with ovarian and breast cancer susceptibility. However, the effects are modest and warrant replication in larger studies. [Cancer Res 2008;68(21):8837–42]
Targeting Melanoma Growth and Metastasis with Systemic Delivery of Liposome-Incorporated Protease-Activated Receptor-1 Small Interfering RNA
Authors: Villares Gabriel J. , Zigler Maya , Wang Hua , Melnikova Vladislava O. , Wu Hong , Friedman Ran , Leslie Michael C. , Vivas-Mejia Pablo E. , Lopez-Berestein Gabriel , Sood Anil K. , Bar-Eli Menashe 
Published: October 2008

AbstractThe thrombin receptor [protease-activated receptor-1 (PAR-1)] is overexpressed in highly metastatic melanoma cell lines and in patients with metastatic lesions. Activation of PAR-1 leads to cell signaling and up-regulation of genes involved in adhesion, invasion, and angiogenesis. Herein, we stably silence PAR-1 through the use of lentiviral short hairpin RNA and found significant decreases in both tumor growth (P &lt; 0.01) and metastasis (P &lt; 0.001) of highly metastatic melanoma cell lines in vivo. The use of viruses for therapy is not ideal as it can induce toxic immune responses and possible gene alterations following viral integration. Therefore, we also used systemic delivery of PAR-1 small interfering RNA (siRNA) incorporated into neutral liposomes [1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC)] to decrease melanoma growth and metastasis in vivo. Significant decreases in tumor growth, weight, and metastatic lung colonies (P &lt; 0.001 for all) were found in mice treated with PAR-1 siRNA-DOPC. The in vivo effects of PAR-1 on invasion and angiogenesis were analyzed via immunohistochemistry. Concomitant decreases in vascular endothelial growth factor, interleukin-8, and matrix metalloproteinase-2 expression levels, as well as decreased blood vessel density (CD31), were found in tumor samples from PAR-1 siRNA-treated mice, suggesting that PAR-1 is a regulator of melanoma cell growth and metastasis by affecting angiogenic and invasive factors. We propose that siRNA incorporated into DOPC nanoparticles could be delivered systemically and used as a new modality for melanoma treatment. [Cancer Res 2008;68(21):9078–86]
Activation of Matrix Metalloproteinase-2 (MMP-2) by Membrane Type 1 Matrix Metalloproteinase through an Artificial Receptor for ProMMP-2 Generates Active MMP-2
Authors: Nishida Yuki , Miyamori Hisashi , Thompson Erik W. , Takino Takahisa , Endo Yoshio , Sato Hiroshi 
Published: October 2008

Abstract
The suggested model for pro-matrix metalloproteinase-2 (proMMP-2) activation by membrane type 1 MMP (MT1-MMP) implicates the complex between MT1-MMP and tissue inhibitor of MMP-2 (TIMP-2) as a receptor for proMMP-2. To dissect this model and assess the pathologic significance of MMP-2 activation, an artificial receptor for proMMP-2 was created by replacing the signal sequence of TIMP-2 with cytoplasmic/transmembrane domain of type II transmembrane mosaic serine protease (MSP-T2). Unlike TIMP-2, MSP-T2 served as a receptor for proMMP-2 without inhibiting MT1-MMP, and generated TIMP-2–free active MMP-2 even at a low level of MT1-MMP. Thus, MSP-T2 did not affect direct cleavage of the substrate testican-1 by MT1-MMP, whereas TIMP-2 inhibited it even at the level that stimulates proMMP-2 processing. Expression of MSP-T2 in HT1080 cells enhanced MMP-2 activation by endogenous MT1-MMP and caused intensive hydrolysis of collagen gel. Expression of MSP-T2 in U87 glioma cells, which express a trace level of endogenous MT1-MMP, induced MMP-2 activation and enhanced cell-associated protease activity, activation of extracellular signal–regulated kinase, and metastatic ability into chick embryonic liver and lung. MT1-MMP can exert both maximum MMP-2 activation and direct cleavage of substrates with MSP-T2, which cannot be achieved with TIMP-2. These results suggest that MMP-2 activation by MT1-MMP potentially amplifies protease activity, and combination with direct cleavage of substrate causes effective tissue degradation and enhances tumor invasion and metastasis, which highlights the complex role of TIMP-2. MSP-T2 is a unique tool to analyze physiologic and pathologic roles of MMP-2 and MT1-MMP in comparison with TIMP-2. [Cancer Res 2008;68(21):9096–104]
CCCTC-Binding Factor Confines the Distal Action of Estrogen Receptor
Authors: Chan Chang S. , Song Jun S. 
Published: October 2008

Abstract
Distal enhancers have recently emerged as a common mode of gene regulation for several transcription factors, including estrogen and androgen receptors, the two key regulators of breast and prostate cancer major subtypes. Despite the rapid success in genome-wide annotation of estrogen receptor-α (ERα) binding sites in cell lines, the precise mechanism governing the gene-to-enhancer association is still unknown and no quantitative model that can predict the estrogen responsiveness of genes has been hitherto proposed. This article presents an integrative genomics approach to construct a predictive model that can explain more than 70% of estrogen-induced expression profiles. The proposed method combines a recent map of the insulator protein CCCTC-binding factor (CTCF) with previous ER location studies and expression profiling in the presence of the translation inhibitor cycloheximide, providing evidence that CTCF partitions the human genome into distinct ER-regulatory blocks. It is shown that estrogen-responsive genes with a decreased transcription level (down-regulated genes) have a markedly different relative distribution of ER binding sites compared with those with an increased transcription level (up-regulated genes). Finally, Bayesian belief networks are constructed to quantify the effects of ER-binding distance from genes as well as the insulating effects of CTCF on the estrogen responsiveness of genes. This work thus represents a stride toward understanding and predicting the distal activities of steroid hormone nuclear receptors. [Cancer Res 2008;68(21):9041–9]
Aurora Kinase A Inhibition Leads to p73-Dependent Apoptosis in p53-Deficient Cancer Cells
Authors: Dar Altaf A. , Belkhiri Abbes , Ecsedy Jeffrey , Zaika Alexander , El-Rifai Wael 
Published: October 2008

Abstract
We investigated the role of Aurora kinase A (AURKA) in regulating p73-dependent apoptosis using the p53-deficient cancer cell lines H1299, TE7, and HCT116p53−/−. Overexpression of AURKA led to down-regulation of the TAp73-induced activation of the p53/p73-dependent luciferase reporter plasmid (pG13-luc). The reduction in the TAp73 transcription activity was confirmed by measuring the activity of luciferase reporters for p21/WAF1, and PUMA. The siRNA knockdown of endogenous AURKA reversed these effects and Western blot analysis showed a significant increase in the protein level of TAp73 and its downstream transcription targets, PUMA, NOXA, and p21/WAF1. The coexpression of AURKA together with TAp73 inhibited the activation of the pG13-luc, PUMA-luc, and p21/WAF1-luc reporter plasmids with reduction in the protein levels of TAp73 transcription targets. Treatment with AURKA-selective small molecule inhibitor MLN8054 led to a significant increase in the activities of pG13-luc, PUMA-luc, and p21/WAF1-luc reporter plasmids. This effect was accompanied by a significant increase in the mRNA and protein levels of several TAp73 transcription targets: p21/WAF1, PUMA, and NOXA. Flow cytometry cell cycle analysis, after MLN8054 treatment, showed more than a 2-fold increase in cell death. The apoptotic outcome was corroborated by showing an increase in cleaved caspase-3 protein levels by Western blot. Using terminal deoxynucleotidyl-transferase–mediated dUTP nick-end labeling assay, we showed that the expression of dominant-negative mutant TAp73 expression plasmid (p73DD) counteracted the MLN8054-induced cell death. Taken together, our results indicate that AURKA regulates TAp73-dependent apoptosis and highlight the potential of the AURKA inhibitor MLN8054 in treating cancers that are defective in p53 signaling. [Cancer Res 2008;68(21):8998–9004]
Optimization of Decision Making in Multilayer Networks: The Role of Locus Coeruleus
Authors: Shea-Brown Eric , Gilzenrat Mark S. , Cohen Jonathan D. 
Published: October 2008

Previous theoretical work has shown that a single-layer neural network can implement the optimal decision process for simple, two-alternative forced-choice (2AFC) tasks. However, it is likely that the mammalian brain comprises multilayer networks, raising the question of whether and how optimal performance can be approximated in such an architecture. Here, we present theoretical work suggesting that the noradrenergic nucleus locus coeruleus (LC) may help optimize 2AFC decision making in the brain. This is based on the observations that neurons of the LC selectively fire following the presentation of salient stimuli in decision tasks and that the corresponding release of norepinephrine can transiently increase the responsivity, or gain, of cortical processing units. We describe computational simulations that investigate the role of such gain changes in optimizing performance of 2AFC decision making. In the tasks we model, no prior cueing or knowledge of stimulus onset time is assumed. Performance is assessed in terms of the rate of correct responses over time (the reward rate). We first present the results of a single-layer model that accumulates (integrates) sensory input and implements the decision process as a threshold crossing. Gain transients, representing the modulatory effect of the LC, are driven by separate threshold crossings in this layer. We optimize over all free parameters to determine the maximum reward rate achievable by this model and compare it to the maximum reward rate when gain is held fixed. We find that the dynamic gain mechanism yields no improvement in reward for this single-layer model. We then examine a two-layer model, in which competing sensory accumulators in the first layer (capable of implementing the task relevant decision) pass activity to response accumulators in a second layer. Again, we compare a version in which threshold crossing in the first (decision) layer elicits an LC response (and a concomitant increase in gain) with a fixed-gain version of the model. Here, we find that gain transients modeling the LC phasic response yield an improvement in reward rate of 12% to 24%. Furthermore, we show that the timing characteristics of these gain transients agree with observations concerning LC firing patterns reported in recent experimental studies. This provides converging evidence for the hypothesis that the LC optimizes processes underlying 2AFC decision making in multilayer networks.
Genetic diversity in the gecko Tarentola mauritanica within the Iberian Peninsula
Authors: Harris David James , Perera Ana 
Published: October 2008

AbstractThe Mediterranean gecko Tarentola mauritanica is one of the most abundant reptile species in the western Mediterranean Basin. We use mitochondrial DNA sequences, 12sRNA and 16sRNA, to analyse the patterns of distribution in the Iberian Peninsula. The results show three well defined lineages. The first one, already known to be widespread throughout Europe, is distributed along the eastern coast and southern areas of the Iberian Peninsula. The second one, endemic to the Iberian Peninsula, is widely found in central regions; and the third lineage, found so far only in two southern localities is unrelated to the other Iberian lineages, but rather to a Northern Moroccan clade. The genetic variability found within the Iberian haplogroup and the existence of a single haplotype within the European lineage suggests a complex pattern of rapid radiations and anthropogenic introductions. The third clade seems to be the result of a natural colonization from North Africa. All the data indicate that T. mauritanica is a species complex. The Iberian Peninsula, due to its geological complex history, appears to be both a hotspot and a melting pot of biodiversity, with several studies of diverse herpetofauna indicating that cryptic species occur there. More studies of additional species will be needed to develop a comparative phylogeographic framework for the region.
Polyandry in Podocnemis unifilis (Pleurodira; Podocnemididae), the vulnerable yellow-spotted Amazon River turtle
Authors: Fantin Cleiton , Farias Izeni Pires , Monjeló Luiz Alberto dos Santos , Viana Luciana Santos 
Published: October 2008

AbstractWe used eight microsatellite loci to investigate the mating system in P. unifilis. DNA samples were collected from 66 hatchlings sampled from six nests on a central Amazon River beach near Barreirinha, Amazonas, Brazil. We found that P. unifilis females exhibited a promiscuous mating system (polyandry) with all nests being fathered by at least two males. The presence of multiple males contributing to each clutch was ascertained by the presence of at least two extra alleles in multilocus genotypes in each nest. Our data demonstrate that polyandry seems to be the prevalent system of mating in this endangered species.
Extreme reduction in body size and reproductive output associated with sandy substrates in two anuran species
Authors: Marangoni Federico , Gomez-Mestre Iván , Tejedo Miguel 
Published: October 2008

AbstractGeographic variation in body size and reproductive traits has been reported in a wide range of organisms, including amphibians. Most studies have focused on latitudinal and/or altitudinal variation where differences in temperature and duration of the growing season are the main causes for population divergence. We describe a steep variation in body size and reproductive traits in two anuran species in southwestern Spain, associated with changes in the geological substrate. Pelobates cultripes and Bufo calamita (= Epidalea calamita) drastically reduced their size (a 71.6% and 76.1% reduction in body mass for P. cultripes and B. calamita, respectively) in just about 60 km. This extreme size reduction was more pronounced at the boundary between two different geological substrates (hercinic and sandy soil). Mean clutch mass, egg size, and clutch size were all smaller in B. calamita populations in the sandy environment. Likewise, clutch mass and egg size were both smaller in sandy P. cultripes populations. We observed a negative correlation between size-adjusted fecundity and egg size for both species, suggesting the existence of a reproductive trade-off that could explain the differences in reproductive allocation between populations and species. In P. cultripes, small-bodied populations had relatively higher fecundities and smaller eggs than large-bodied ones, whereas in B. calamita populations from the sandy area we found both populations with high fecundity and small eggs, and populations with low fecundity and large eggs. Common environmental effects associated with the sandy substrate produce a similar reduction in size in both toad species.
Seasonal changes in reproductive output of a year-round nesting population of the green turtle Chelonia mydas at Huyong Island, Thailand
Authors: Yasuda Tohya , Kittiwattanawong Kongkiat , Klom-in Winai , Arai Nobuaki 
Published: October 2008

AbstractFor the vast majority of reptiles, low temperature is a major constraint on reproduction. However, continuous reproduction is not always observed even in equatorial climates. In the present study, we examined the reproductive output of green turtles in a year-round nesting population on Huyong Island, Thailand. From 1996 to 2007, 121 females were identified. Because individual turtles nest several times within a season, we defined the nesting season of an individual as the month during which the first nesting activity was detected. We found a significant difference in clutch frequency among months. However, there were no significant relationships during the nesting period between clutch frequency and environmental parameters such as mean daily air temperature, precipitation and maximum wind speed. Although we could not identify the specific factors, our findings suggest that environmental factors may regulate seasonal variation in reproductive output even in the tropics.
Typhlophis ayarzaguenai Señaris, 1998 is a junior synonym of Typhlophis squamosus (Schlegel, 1839)
Authors: Kok Philippe , Fuenmayor Gilson Rivas 
Published: October 2008

AbstractIn 1839, Schlegel described Typhlophis squamosus on the basis of a single specimen from Cayenne, French Guiana. Since then the species has been reported from Brazil, Guyana and Suriname. Relying only on the original description and a subsequent short description of the holotype of T. squamosus by Boulenger in 1893, Señaris described T. ayarzaguenai from Venezuela in 1998. Señaris' description of T. ayarzaguenai contains several errors and discrepancies and we argue that our observations justify the consideration of T. ayarzaguenai as a junior synonym of T. squamosus. The genus Typhlophis thus remains monotypic and T. squamosus is a widespread species in the Guiana Shield.
Interactions between freshwater mussels and newts: a novel form of parasitism?
Authors: Engel Edmée , Groh Klaus , Griffiths Richard , Wood Laura , Schley Laurent 
Published: October 2008

AbstractSmall freshwater mussels are sometimes found attached to the toes of aquatic phase amphibians, but the ecological implications of this interspecific relationship are unknown. Toe condition and mussel presence were recorded for newts caught in 37 ponds in Luxembourg between March and June 2007. All four local newt species were affected (Lissotriton helveticus, L. vulgaris, Mesotriton alpestris and Triturus cristatus), primarily by the mussel Sphaerium nucleus but also by Pisidium subtruncatum. Mussel attachment was observed in three ponds, with a particularly high occurrence in one pond, where 23% of newts were affected and significantly more toes were damaged than in other ponds. Mussels caused local tissue and bone damage to their host and may interfere with egg-laying. Twenty-two newts with attached mussels were observed in aquaria for up to 3 days: 13 mussels detached when the newt's toe fell off and nine remained attached. If the mussels benefit from the interaction through, for example, enhanced dispersal then the relationship between the two taxa represents a novel form of parasitism.
Short-term changes in dorsal reflectance for background matching in Ornate Tree Lizards (Urosaurus ornatus)
Authors: Hamilton Paul , Sullivan Brian , Gaalema Diann 
Published: October 2008

AbstractSome lizards are thought to exhibit short-term changes in color to match their background, but this ability has not been verified empirically. We tested the hypothesis that lizards will change dorsal reflectance over a series of days to match their backgrounds. We housed male and female Ornate Tree Lizards (Urosaurus ornatus) for five days in aquaria painted to match environmental extremes in substrate reflectance. Standardized photographs were taken each day yielding dorsal percent reflectance values. After the first day, reflectance of lizards changed significantly to more closely match their backgrounds; this effect became more pronounced through the fifth and final day of the experiment.
Links between Tropical Pacific SST and Cholera Incidence in Bangladesh: Role of the Western Tropical and Central Extratropical Pacific
Authors: Cash Benjamin A. , Rodó Xavier , Kinter James L. 
Published: October 2008

Abstract
Recent studies arising from both statistical analysis and dynamical disease models demonstrate a link between the incidence of cholera, a paradigmatic waterborne bacterial illness endemic to Bangladesh, and the El Niño–Southern Oscillation (ENSO). The physical significance of this relationship was investigated by examining links between the regional climate of Bangladesh and western Pacific sea surface temperatures (SST) associated with ENSO using a pacemaker configuration of the Center for Ocean–Land–Atmosphere Studies atmospheric general circulation model. The global SST response to ENSO SST anomalies in the western Pacific alone is found to be relatively weak and unrealistic when compared to observations, indicating that the global response to ENSO is driven primarily by anomalies in the central and eastern tropical Pacific. Despite the weak global response to western Pacific SST anomalies, however, a signal is found in summer rainfall over India and Bangladesh. Specifically, reduced rainfall typically follows winter El Niño events. In the absence of warm SST anomalies in the eastern Pacific, cold anomalies in the western Pacific produce a La Niña–like response in the model circulation. Cold SST anomalies suppress convection over the western Pacific. Large-scale convergence shifts into the eastern Indian Ocean and modifies the summer monsoon circulation over India and Bangladesh.
The probabilistic relationship between Bangladesh rainfall and SST is also explored using a nonparametric statistical technique. Decreased rainfall is strongly associated with cold SST in the western Pacific, while associations between SST and enhanced rainfall are substantially weaker. Also found are strong associations between rainfall and SST in the Indian Ocean in the absence of differences in forcing from the western Pacific. It thus appears that the Indian Ocean may represent an independent source of predictability for the monsoon and cholera risk. Likewise, under certain circumstances, the western Pacific may also exert a significant influence on Bangladesh rainfall and cholera risk.