Systematic identification of transcription factors associated with patient survival in cancers

<p>Abstract</p> <p>Background</p> <p>Aberrant activation or expression of transcription factors has been implicated in the tumorigenesis of various types of cancer. In spite of the prevalent application of microarray experiments for profiling gene expression in cancer samples, they provide limited information regarding the activities of transcription factors. However, the association between transcription factors and cancers is largely dependent on the transcription regulatory activities rather than mRNA expression levels.</p> <p>Results</p> <p>In this paper, we propose a computational approach that integrates microarray expression data with the transcription factor binding site information to systematically identify transcription factors associated with patient survival given a specific cancer type. This approach was applied to two gene expression data sets for breast cancer and acute myeloid leukemia. We found that two transcription factor families, the steroid nuclear receptor family and the ATF/CREB family, are significantly correlated with the survival of patients with breast cancer; and that a transcription factor named T-cell acute lymphocytic leukemia 1 is significantly correlated with acute myeloid leukemia patient survival.</p> <p>Conclusion</p> <p>Our analysis identifies transcription factors associating with patient survival and provides insight into the regulatory mechanism underlying the breast cancer and leukemia. The transcription factors identified by our method are biologically meaningful and consistent with prior knowledge. As an insightful tool, this approach can also be applied to other microarray cancer data sets to help researchers better understand the intricate relationship between transcription factors and diseases.</p

A symplectic dynamics approach to the spatial isosceles three-body problem

We study the spatial isosceles three-body problem from the perspective of Symplectic Dynamics. For certain choices of mass ratio, angular momentum, and energy, the dynamics on the energy surface is equivalent to a Reeb flow on the tight three-sphere. We find a Hopf link formed by the Euler orbit and a symmetric brake orbit, which spans an open book decomposition whose pages are annulus-like global surfaces of section. In the case of large mass ratios, the Hopf link is non-resonant, forcing the existence of infinitely many periodic orbits. The rotation number of the Euler orbit plays a fundamental role in the existence of periodic orbits and their symmetries. We explore such symmetries in the Hill region and show that the Euler orbit is negative hyperbolic for an open set of parameters while it can never be positive hyperbolic. Finally, we address convexity and determine for each parameter whether the energy surface is strictly convex, convex, or non-convex. Dynamical consequences of this fact are then discussed.Comment: 66 pages, 15 figure

Maintaining Soft Arc Consistency in BnB-ADOPT+ During Search

Gutierrez and Meseguer show how to enforce consistency in BnB-ADOPT + for distributed constraint optimization, but they consider unconditional deletions only. However, during search, more values can be pruned conditionally according to variable instantiations that define subproblems. Enforcing consistency in these subproblems can cause further search space reduction. We introduce efficient methods to maintain soft arc consistencies in every subproblem during search, a non trivial task due to asynchronicity and induced overheads. Experimental results show substantial benefits on three different benchmarks. © 2013 Springer-Verlag.The work of Gutierrez and Meseguer was partially supported by the Spanish project TIN2009-13591-C02-02 and Generalitat de Catalunya 2009-SGR-1434.Peer Reviewe

JNK regulates compliance-induced adherens junctions formation in epithelial cells and tissues

We demonstrate that c-Jun N-terminal kinase (JNK) responds to substrate stiffness and regulates adherens junction (AJ) formation in epithelial cells in 2D cultures and in 3D tissues in vitro and in vivo. Rigid substrates led to JNK activation and AJ disassembly, whereas soft matrices suppressed JNK activity leading to AJ formation. Expression of constitutively active JNK (MKK7-JNK1) induced AJ dissolution even on soft substrates, whereas JNK knockdown (using shJNK) induced AJ formation even on hard substrates. In human epidermis, basal cells expressed phosphorylated JNK but lacked AJ, whereas suprabasal keratinocytes contained strong AJ but lacked phosphorylated JNK. AJ formation was significantly impaired even in the upper suprabasal layers of bioengineered epidermis when prepared with stiffer scaffold or keratinocytes expressing MKK7-JNK1. By contrast, shJNK1 or shJNK2 epidermis exhibited strong AJ even in the basal layer. The results with bioengineered epidermis were in full agreement with the epidermis of jnk1(-/-) or jnk2(-/-) mice. In conclusion, we propose that JNK mediates the effects of substrate stiffness on AJ formation in 2D and 3D contexts in vitro as well as in vivo

Redisposition of acremonium-like fungi in Hypocreales

Acremonium is acknowledged as a highly ubiquitous genus including saprobic, parasitic, or endophytic fungi that inhabit a variety of environments. Species of this genus are extensively exploited in industrial, commercial, pharmaceutical, and biocontrol applications, and proved to be a rich source of novel and bioactive secondary metabolites. Acremonium has been recognised as a taxonomically difficult group of ascomycetes, due to the reduced and high plasticity of morphological characters, wide ecological distribution and substrate range. Recent advances in molecular phylogenies, revealed that Acremonium is highly polyphyletic and members of Acremonium s. lat. belong to at least three distinct orders of Sordariomycetes, of which numerous orders, families and genera with acremonium-like morphs remain undefined. To infer the phylogenetic relationships and establish a natural classification for acremonium-like taxa, systematic analyses were conducted based on a large number of cultures with a global distribution and varied substrates. A total of 633 cultures with acremonium-like morphology, including 261 ex-type cultures from 89 countries and a variety of substrates including soil, plants, fungi, humans, insects, air, and water were examined. An overview phylogenetic tree based on three loci (ITS, LSU, rpb2) was generated to delimit the orders and families. Separate trees based on a combined analysis of four loci (ITS, LSU, rpb2, tef-1α) were used to delimit species at generic and family levels. Combined with the morphological features, host associations and ecological analyses, acremonium-like species evaluated in the present study are currently assigned to 63 genera, and 14 families in Cephalothecales, Glomerellales and Hypocreales, mainly in the families Bionectriaceae, Plectosphaerellaceae and Sarocladiaceae and five new hypocrealean families, namely Chrysonectriaceae, Neoacremoniaceae, Nothoacremoniaceae, Pseudoniessliaceae and Valsonectriaceae. Among them, 17 new genera and 63 new combinations are proposed, with descriptions of 65 new species. Furthermore, one epitype and one neotype are designated to stabilise the taxonomy and use of older names. Results of this study demonstrated that most species of Acremonium s. lat. grouped in genera of Bionectriaceae, including the type A. alternatum. A phylogenetic backbone tree is provided for Bionectriaceae, in which 183 species are recognised and 39 well-supported genera are resolved, including 10 new genera. Additionally, rpb2 and tef-1α are proposed as potential DNA barcodes for the identification of taxa in Bionectriaceae

Developmental Exposure to a Commercial PBDE Mixture: Effects on Protein Networks in the Cerebellum and Hippocampus of Rats

Background: Polybrominated diphenyl ethers (PBDEs) are structurally similar to polychlorinated biphenyls (PCBs) and have both central (learning and memory deficits) and peripheral (motor dysfunction) neurotoxic effects at concentrations/doses similar to those of PCBs. The cellular and molecular mechanisms for these neurotoxic effects are not fully understood; however, several studies have shown that PBDEs affect thyroid hormones, cause oxidative stress, and disrupt Ca2+-mediated signal transduction. Changes in these signal transduction pathways can lead to differential gene regulation with subsequent changes in protein expression, which can affect the development and function of the nervous system

WHISTLE server: A high-accuracy genomic coordinate-based machine learning platform for RNA modification prediction

The primary sequences of DNA, RNA and protein have been used as the dominant information source of existing machine learning tools, especially for contexts not fully explored by wet-experimental approaches. Since molecular markers are profoundly orchestrated in the living organisms, those markers that cannot be unambiguously recovered from the primary sequence often help to predict other biological events. To the best of our knowledge, there is no current tool to build and deploy machine learning models that consider genomic evidence. We therefore developed the WHISTLE server, the first machine learning platform based on genomic coordinates. It features convenient covariate extraction and model web deployment with 46 distinct genomic features integrated along with the conventional sequence features. We showed that, when predicting m6A sites from SRAMP project, the model integrating genomic features substantially outperformed those based on only sequence features. The WHISTLE server should be a useful tool for studying biological attributes specifically associated with genomic coordinates, and is freely accessible at: www.xjtlu.edu.cn/biologicalsciences/whi2