bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interplay between neural-cadherin and vascular endothelial-cadherin in breast cancer progression
Authors: Rezaei Maryam , Friedrich Katrin , Wielockx Ben , Kuzmanov Aleksandar , Kettelhake Antje , Labelle Myriam , Schnittler Hans , Baretton Gustavo , Breier Georg 
Published: December 2012

Abstract
Introduction
Deregulation of cadherin expression, in particular the loss of epithelial (E)-cadherin and gain of neural (N)-cadherin, has been implicated in carcinoma progression. We previously showed that endothelial cell-specific vascular endothelial (VE)-cadherin can be expressed aberrantly on tumor cells both in human breast cancer and in experimental mouse mammary carcinoma. Functional analyses revealed that VE-cadherin promotes tumor cell proliferation and invasion by stimulating transforming growth factor (TGF)-β signaling. Here, we investigate the functional interplay between N-cadherin and VE-cadherin in breast cancer.

Methods
The expression of N-cadherin and VE-cadherin was evaluated by immunohistochemistry in a tissue microarray with 84 invasive human breast carcinomas. VE-cadherin and N-cadherin expression in mouse mammary carcinoma cells was manipulated by RNA interference or overexpression, and cells were then analyzed by immunofluorescence, reverse transcriptase-polymerase chain reaction, and western blot. Experimental tumors were generated by transplantation of the modified mouse mammary carcinoma cells into immunocompetent mice. Tumor growth was monitored, and tumor tissue was subjected to histological analysis.

Results
VE-cadherin and N-cadherin were largely co-expressed in invasive human breast cancers. Silencing of N-cadherin in mouse mammary carcinoma cells led to decreased VE-cadherin expression and induced changes indicative of mesenchymal-epithelial transition, as indicated by re-induction of E-cadherin, localization of β-catenin at the cell membrane, decreased expression of vimentin and SIP1, and gain of epithelial morphology. Suppression of N-cadherin expression also inhibited tumor growth in vivo, even when VE-cadherin expression was forced.

Conclusions
Our results highlight the critical role of N-cadherin in breast cancer progression and show that N-cadherin is involved in maintaining the malignant tumor cell phenotype. The presence of N-cadherin prevents the re-expression of E-cadherin and localization of β-catenin at the plasma membrane of mesenchymal mammary carcinoma cells. N-cadherin is also required to maintain the expression of VE-cadherin in malignant tumor cells but not vice versa. Thus, N-cadherin acts in concert with VE-cadherin to promote tumor growth.
Novel mechanism for mesenchymal stem cells in attenuating peritoneal adhesion: accumulating in the lung and secreting tumor necrosis factor α-stimulating gene-6
Authors: Wang Nan , Shao Yeqing , Mei Yan , Zhang Li , Li Qinggang , Li Diangeng , Shi Suozhu , Hong Quan , Lin Hongli , Chen Xiangmei 
Published: December 2012

Abstract
Introduction
We previously found that mesenchymal stem cells (MSCs) injected intravenously could attenuate peritoneal adhesion by secreting tumor necrosis alpha-stimulating gene (TSG)-6, while MSCs injected intraperitoneally could not. However, the underlying mechanism remains unclear. This study was designed to investigate the means by which MSCs exert their effects.

Methods
Rat bone marrow-derived MSCs/red fluorescent protein (RFP) were injected either intraperitoneally or intravenously into Sprague-Dawley (SD) rats at different time points after peritoneal scraping. Peritoneal adhesions were evaluated macroscopically at day 14 after scraping. The distribution of MSCs injected intraperitoneally or intravenously was traced by two-photon fluorescence confocal imaging and immunofluorescence microscopy. The co-localization of MSCs and macrophages in the lung and the spleen, and the expression of TSG-6 in MSCs trapped in the lung or the spleen were evaluated by immunofluorescence microscopy. The concentration of TSG-6 in serum was evaluated by ELISA. After intravenous injection of TSG-6- small interfering (si) RNA-MSCs, the expression of TSG-6 in MSCs and the concentration of TSG-6 in serum were reevaluated, and peritoneal adhesions were evaluated macroscopically and histologically.

Results
MSCs injected intraperitoneally failed to reduce peritoneal adhesion, and MSCs injected intravenously markedly improved peritoneal adhesion. Two-photon fluorescence confocal imaging showed that MSCs injected intravenously accumulated mainly in the lung, where they remained for seven days, and immunofluorescence microscopy showed few MSCs phagocytosed by macrophages. In contrast, large numbers of MSCs accumulated in the spleen with obvious phagocytosis by macrophages even at 4 hours after intraperitoneal injection. Immunofluorescence microscopy showed that MSCs that accumulated in the lung after intravenous injection could express TSG-6 within 12 hours, but TSG-6-siRNA-MSCs or MSCs accumulated in the spleen after intraperitoneal injection did not. ELISA showed that the concentration of TSG-6 in serum was increased at 4 hours after intravenous injection of MSCs, while there was no increase after injection of TSG-6-siRNA-MSCs or after intraperitoneal injection of MSCs. Moreover, intravenous injection of TSG-6-siRNA-MSCs failed to attenuate peritoneal adhesion.

Conclusions
Our findings suggest that intravenously injected MSCs accumulated in the lung and attenuated peritoneal adhesion by secreting TSG-6, but intraperitoneally injected MSCs were phagocytosed by macrophages in the spleen and failed to attenuate peritoneal adhesion.
The armadillo: a model for neuropathy of leprosy and potentially other neurodegenerative diseases
Authors: Sharma Rahul , Lahiri Ramanuj , Scollard David M. , Pena Maria , Williams Diana L. , Adams Linda B. , Figarola John , Truman Richard W. 
Published: December 2012

SummaryLeprosy (also known as Hansen's disease) is an infectious peripheral neurological disorder caused by Mycobacterium leprae that even today leaves millions of individuals worldwide with life-long disabilities. The specific mechanisms by which this bacterium induces nerve injury remain largely unknown, mainly owing to ethical and practical limitations in obtaining affected human nerve samples. In addition to humans, nine-banded armadillos (Dasypus novemcinctus) are the only other natural host of M. leprae, and they develop a systemically disseminated disease with extensive neurological involvement. M. leprae is an obligate intracellular parasite that cannot be cultivated in vitro. Because of the heavy burdens of bacilli they harbor, nine-banded armadillos have become the organism of choice for propagating large quantities of M. leprae, and they are now advancing as models of leprosy pathogenesis and nerve damage. Although armadillos are exotic laboratory animals, the recently completed whole genome sequence for this animal is enabling researchers to undertake more sophisticated molecular studies and to develop armadillo-specific reagents. These advances will facilitate the use of armadillos in piloting new therapies and diagnostic regimens, and will provide new insights into the oldest known infectious neurodegenerative disorder.
Applications of Normal Coordinates of Internal Vibrations to Generate Perturbed Structures: Dynamic Behavior of Weak to Strong Interactions Elucidated by Atoms-in-Molecules Dual Functional Analysis
Authors: Nakanishi Waro , Hayashi Satoko , Matsuiwa Kohei , Kitamoto Masayuki 
Published: December 2012

Abstract
Normal coordinates of internal vibrations (NIV) are employed to generate the perturbed structures necessary in the atoms-in-molecules (AIM) dual functional analysis for a wide range of weak to strong interactions. Hb(rc) are plotted versus Hb(rc) − Vb(rc)/2 [= (2/8m)∇2ρb(rc)] at bond critical points in the treatment, which incorporates the classification of interactions by signs of ∇2ρb(rc) and Hb(rc). The plots are analyzed using the polar (R, θ) representation. Each plot for an interaction shows a specific curve, which is expressed by (θp, κp): θp corresponds to the tangent line for the plot measured from the y-direction and κp is the curvature. While (R, θ) correspond to the static behavior of interactions at the fully optimized structures, (θp, κp) exhibit the dynamic nature. The (θp, κp) values evaluated employing the perturbed structures with NIV are shown to be very close to those obtained using perturbed structures partially optimized with the distances in question being fixed suitably (POM). The magnitudes of differences in θp and κp between those evaluated with NIV and POM are ≤2° and ≤2 au−1, respectively, for usual interactions. It is demonstrated that NIV is applicable to wide range of usual interactions, as well as POM.
Novel Use of Derived Genotype Probabilities to Discover Significant Dominance Effects for Milk Production Traits in Dairy Cattle
Authors: Boysen Teide-Jens , Heuer Claas , Tetens Jens , Reinhardt Fritz , Thaller Georg 
Published: December 2012

Abstract
The estimation of dominance effects requires the availability of direct phenotypes, i.e., genotypes and phenotypes in the same individuals. In dairy cattle, classical QTL mapping approaches are, however, relying on genotyped sires and daughter-based phenotypes like breeding values. Thus, dominance effects cannot be estimated. The number of dairy bulls genotyped for dense genome-wide marker panels is steadily increasing in the context of genomic selection schemes. The availability of genotyped cows is, however, limited. Within the current study, the genotypes of male ancestors were applied to the calculation of genotype probabilities in cows. Together with the cows’ phenotypes, these probabilities were used to estimate dominance effects on a genome-wide scale. The impact of sample size, the depth of pedigree used in deriving genotype probabilities, the linkage disequilibrium between QTL and marker, the fraction of variance explained by the QTL, and the degree of dominance on the power to detect dominance were analyzed in simulation studies. The effect of relatedness among animals on the specificity of detection was addressed. Furthermore, the approach was applied to a real data set comprising 470,000 Holstein cows. To account for relatedness between animals a mixed-model two-step approach was used to adjust phenotypes based on an additive genetic relationship matrix. Thereby, considerable dominance effects were identified for important milk production traits. The approach might serve as a powerful tool to dissect the genetic architecture of performance and functional traits in dairy cattle.
On the Statistical Interpretation of Site-Specific Variables in Phylogeny-Based Substitution Models
Authors: Rodrigue Nicolas 
Published: December 2012

Abstract
Phylogeny-based modeling of heterogeneity across the positions of multiple-sequence alignments has generally been approached from two main perspectives. The first treats site specificities as random variables drawn from a statistical law, and the likelihood function takes the form of an integral over this law. The second assigns distinct variables to each position, and, in a maximum-likelihood context, adjusts these variables, along with global parameters, to optimize a joint likelihood function. Here, it is emphasized that while the first approach directly enjoys the statistical guaranties of traditional likelihood theory, the latter does not, and should be approached with particular caution when the site-specific variables are high dimensional. Using a phylogeny-based mutation-selection framework, it is shown that the difference in interpretation of site-specific variables explains the incongruities in recent studies regarding distributions of selection coefficients.
Genetic Diversity and the Structure of Genealogies in Rapidly Adapting Populations
Authors: Desai Michael M , Walczak Aleksandra M , Fisher Daniel S 
Published: December 2012

Abstract
Positive selection distorts the structure of genealogies and hence alters patterns of genetic variation within a population. Most analyses of these distortions focus on the signatures of hitchhiking due to hard or soft selective sweeps at a single genetic locus. However, in linked regions of rapidly adapting genomes, multiple beneficial mutations at different loci can segregate simultaneously within the population, an effect known as clonal interference. This leads to a subtle interplay between hitchhiking and interference effects, which leads to a unique signature of rapid adaptation on genetic variation both at the selected sites and at linked neutral loci. Here, we introduce an effective coalescent theory (a “fitness-class coalescent”) that describes how positive selection at many perfectly linked sites alters the structure of genealogies. We use this theory to calculate several simple statistics describing genetic variation within a rapidly adapting population and to implement efficient backward-time coalescent simulations, which can be used to predict how clonal interference alters the expected patterns of molecular evolution.
A Connected Set of Genes Associated with Programmed Cell Death Implicated in Controlling the Hypersensitive Response in Maize
Authors: Olukolu Bode A , Negeri Adisu , Dhawan Rahul , Venkata Bala P , Sharma Pankaj , Garg Anshu , Gachomo Emma , Marla Sandeep , Chu Kevin , Hasan Anna , Ji Jiabing , Chintamanani Satya , Green Jason , Shyu Chi-Ren , Wisser Randall , Holland James , Johal Guri , Balint-Kurti Peter 
Published: December 2012

Abstract
Rp1-D21 is a maize auto-active resistance gene conferring a spontaneous hypersensitive response (HR) of variable severity depending on genetic background. We report an association mapping strategy based on the Mutant Assisted Gene Identification and Characterization approach to identify naturally occurring allelic variants associated with phenotypic variation in HR. Each member of a collection of 231 diverse inbred lines of maize constituting a high-resolution association mapping panel were crossed to a parental stock heterozygous for Rp1-D21, and the segregating F1 generation testcrosses were evaluated for phenotypes associated with lesion severity for 2 years at two locations. A genome-wide scan for associations with HR was conducted with 47,445 SNPs using a linear mixed model that controlled for spurious associations due to population structure. Since the ability to identify candidate genes and the resolution of association mapping are highly influenced by linkage disequilibrium (LD), we examined the extent of genome-wide LD. On average, marker pairs separated by &gt;10 kbp had an r2 value of &lt;0.1. Genomic regions surrounding SNPs significantly associated with HR traits were locally saturated with additional SNP markers to establish local LD structure and precisely identify candidate genes. Six significantly associated SNPs at five loci were detected. At each locus, the associated SNP was located within or immediately adjacent to candidate causative genes predicted to play significant roles in the control of programmed cell death and especially in ubiquitin pathway-related processes.
Genomic Prediction in Animals and Plants: Simulation of Data, Validation, Reporting, and Benchmarking
Authors: Daetwyler Hans D , Calus Mario P L , Pong-Wong Ricardo , de los Campos Gustavo , Hickey John M 
Published: December 2012

AbstractThe genomic prediction of phenotypes and breeding values in animals and plants has developed rapidly into its own research field. Results of genomic prediction studies are often difficult to compare because data simulation varies, real or simulated data are not fully described, and not all relevant results are reported. In addition, some new methods have been compared only in limited genetic architectures, leading to potentially misleading conclusions. In this article we review simulation procedures, discuss validation and reporting of results, and apply benchmark procedures for a variety of genomic prediction methods in simulated and real example data. Plant and animal breeding programs are being transformed by the use of genomic data, which are becoming widely available and cost-effective to predict genetic merit. A large number of genomic prediction studies have been published using both simulated and real data. The relative novelty of this area of research has made the development of scientific conventions difficult with regard to description of the real data, simulation of genomes, validation and reporting of results, and forward in time methods. In this review article we discuss the generation of simulated genotype and phenotype data, using approaches such as the coalescent and forward in time simulation. We outline ways to validate simulated data and genomic prediction results, including cross-validation. The accuracy and bias of genomic prediction are highlighted as performance indicators that should be reported. We suggest that a measure of relatedness between the reference and validation individuals be reported, as its impact on the accuracy of genomic prediction is substantial. A large number of methods were compared in example simulated and real (pine and wheat) data sets, all of which are publicly available. In our limited simulations, most methods performed similarly in traits with a large number of quantitative trait loci (QTL), whereas in traits with fewer QTL variable selection did have some advantages. In the real data sets examined here all methods had very similar accuracies. We conclude that no single method can serve as a benchmark for genomic prediction. We recommend comparing accuracy and bias of new methods to results from genomic best linear prediction and a variable selection approach (e.g., BayesB), because, together, these methods are appropriate for a range of genetic architectures. An accompanying article in this issue provides a comprehensive review of genomic prediction methods and discusses a selection of topics related to application of genomic prediction in plants and animals.
How Does the Incentive Effect of the Charitable Deduction Vary across Charities?
Authors: Yetman Michelle H. , Yetman Robert J. 
Published: December 2012

ABSTRACT:
We examine how taxes affect donations given to nonprofit organizations and how this varies across nonprofit types. Most prior studies constrained tax price elasticities to be constant across nonprofits, primarily because the data do not provide donations by nonprofit type. Using nonprofit-level data and average marginal tax rates that vary across years and states, we estimate tax price elasticities by nonprofit type. We find an aggregate public charity elasticity of approximately −1.0 and a private foundation elasticity of approximately −2.0. These results suggest that the cost of the charitable contribution deduction is roughly proportional to its benefit for public charities, but that the deduction stimulates significant giving for private foundations. When we partition our elasticities across 24 public charity types, we find significant elasticities of −1.0 or larger for six types. This result suggests that the effect of the charitable contribution deduction varies significantly across nonprofit types.
JEL Classifications: H2; H4; H7; L3; K34
Data Availability: The data are available from public sources identified in this study.
Client Risk Management: A Pecking Order Analysis of Auditor Response to Upward Earnings Management Risk
Authors: Krishnan Gopal V. , Sun Lili , Wang Qian , Yang Rong 
Published: December 2012

SUMMARY:
This study examines Big N auditors' client risk management strategy in response to the risk of upward (i.e., income-increasing) earnings management in the post-SOX era. Specifically, we empirically study the relation between clients' signed discretionary accruals and subsequent audit pricing and auditor resignation decisions. We find that audit fees and resignations are positively associated with the risk of upward earnings management. We document a pecking order of auditor responses and find that auditors are more likely to respond in the order of charging higher abnormal audit fees if the trade-off between upward earnings management risk and return is within an acceptable level, and then resign if the risk is more severe and exceeds the auditors' tolerance level. Our results are robust to alternative accruals measures, controlling for clients' internal control quality and corporate governance characteristics.
Roger's Dilemma: A Situational Examination of Ethical Behavior in the Presence of Internal Control Deficiencies
Authors: Mellon Mark J. , Marley Robert 
Published: December 2012

ABSTRACT:
This case exposes students to decision making in an ethically and legally ambiguous situation. It also asks them to practice using their ethical sensitivity by identifying situations where ethical conflicts are present. Students will learn the Securities and Exchange Commission's definition of insider trading and gain an understanding of the Supreme Court's recent interpretations regarding the specifics of what constitutes insider trading. Students will also learn about the legal protection afforded to whistleblowers under the Sarbanes-Oxley Act and learn about the code of ethics requirement applicable to public company's senior financial officers and the chief executive officer. Finally, students will be exposed to the definition of an internal control deficiency and learn how to identify two types of internal control deficiencies.
The IFRS Transition and Accounting Education: A Canadian Perspective Post-Transition
Authors: Hilton Sandy R. , Johnstone Nathalie 
Published: December 2012

ABSTRACT
Canada transitioned to International Financial Reporting Standards (IFRS) in 2010–2011. In this commentary, we discuss the impact that the transition had from an accounting education perspective, particularly on undergraduate accounting programs. Our experience was that the transition was not a substantial hurdle but that it did provide opportunity for many formal and informal discussions of the accounting curriculum and pedagogy. Canada also introduced separate accounting standards for private enterprises at the same time as we transitioned to IFRS. Therefore, accounting educators were concerned with potential content overload and strategies for minimizing content overload. In this commentary we discuss both of those issues as well as a third common discussion topic in Canada during the transition—how to teach professional skills to accounting students. This commentary summarizes those three topics that were common in accounting education in Canada during the IFRS transition.