Genomic loss of tumor suppressor miRNA-204 promotes cancer cell migration and invasion by activating AKT/mTOR/Rac1 signaling and actin reorganization

Increasing evidence suggests that chromosomal regions containing microRNAs are functionally important in cancers. Here, we show that genomic loci encoding miR-204 are frequently lost in multiple cancers, including ovarian cancers, pediatric renal tumors, and breast cancers. MiR-204 shows drastically reduced expression in several cancers and acts as a potent tumor suppressor, inhibiting tumor metastasis in vivo when systemically delivered. We demonstrated that miR-204 exerts its function by targeting genes involved in tumorigenesis including brain-derived neurotrophic factor (BDNF), a neurotrophin family member which is known to promote tumor angiogenesis and invasiveness. Analysis of primary tumors shows that increased expression of BDNF or its receptor tropomyosin-related kinase B (TrkB) parallel a markedly reduced expression of miR-204. Our results reveal that loss of miR-204 results in BDNF overexpression and subsequent activation of the small GTPase Rac1 and actin reorganization through the AKT/mTOR signaling pathway leading to cancer cell migration and invasion. These results suggest that microdeletion of genomic loci containing miR-204 is directly linked with the deregulation of key oncogenic pathways that provide crucial stimulus for tumor growth and metastasis. Our findings provide a strong rationale for manipulating miR-204 levels therapeutically to suppress tumor metastasis

Cubic Spline Interpolation Reveals Different Evolutionary Trends of Various Species

Instead of being uniform in each branch of the biological evolutionary tree, the speed of evolution, measured in the number of mutations over a fixed number of years, seems to be much faster or much slower than average in some branches of the evolutionary tree. This paper describes an evolutionary trend discovery algorithm that uses cubic spline interpolation for various branches of the evolutionary tree. As shown in an example, within the vertebrate evolutionary tree, human evolution seems to be currently speeding up while the evolution of chickens is slowing down. The new algorithm can automatically identify those branches and times when something unusual has taken place, aiding data analytics of evolutionary data

Mutations of Adjacent Amino Acid Pairs are not Always Independent

Evolutionary studies usually assume that the genetic mutations are independent of each other. This paper tests the independence hypothesis for genetic mutations with regard to protein coding regions. According to the new experimental results the independence assumption generally holds, but there are certain exceptions. In particular, the coding regions that represent two adjacent amino acids seem to change in ways that sometimes deviate significantly from the expected theoretical probability under the independence assumption

Optimizing Phylogenetic Supertrees Using Answer Set Programming

The supertree construction problem is about combining several phylogenetic trees with possibly conflicting information into a single tree that has all the leaves of the source trees as its leaves and the relationships between the leaves are as consistent with the source trees as possible. This leads to an optimization problem that is computationally challenging and typically heuristic methods, such as matrix representation with parsimony (MRP), are used. In this paper we consider the use of answer set programming to solve the supertree construction problem in terms of two alternative encodings. The first is based on an existing encoding of trees using substructures known as quartets, while the other novel encoding captures the relationships present in trees through direct projections. We use these encodings to compute a genus-level supertree for the family of cats (Felidae). Furthermore, we compare our results to recent supertrees obtained by the MRP method.Comment: To appear in Theory and Practice of Logic Programming (TPLP), Proceedings of ICLP 201

A Computational Study of the Evolution of Cretan and Related Scripts

Crete was the birthplace of several ancient writings, including the Cretan Hieroglyphs, the Linear A and the Linear B scripts. Out of these three only Linear B is deciphered. The sound values of the Cretan Hieroglyph and the Linear A symbols are unknown and attempts to reconstruct them based on Linear B have not been fruitful. In this paper, we compare the ancient Cretan scripts with four other Mediterranean and Black Sea scripts, namely Phoenician, South Arabic, Greek and Old Hungarian. We provide a computational study of the evolution of the three Cretan and four other scripts. This study encompasses a novel translation of the scripts to a DNA encoding, which enables the use of hypothetical evolutionary tree reconstruction algorithms from the area of bioinformatics

A Computational Study of the Evolution of Cretan and Related Scripts

Crete was the birthplace of several ancient writings, including the Cretan Hieroglyphs, the Linear A and the Linear B scripts. Out of these three only Linear B is deciphered. The sound values of the Cretan Hieroglyph and the Linear A symbols are unknown and attempts to reconstruct them based on Linear B have not been fruitful. In this paper, we compare the ancient Cretan scripts with four other Mediterranean and Black Sea scripts, namely Phoenician, South Arabic, Greek and Old Hungarian. We provide a computational study of the evolution of the three Cretan and four other scripts. This study encompasses a novel translation of the scripts to a DNA encoding, which enables the use of hypothetical evolutionary tree reconstruction algorithms from the area of bioinformatics

Intelligent ZHENG Classification of Hypertension Depending on ML-kNN and Information Fusion

Hypertension is one of the major causes of heart cerebrovascular diseases. With a good accumulation of hypertension clinical data on hand, research on hypertension's ZHENG differentiation is an important and attractive topic, as Traditional Chinese Medicine (TCM) lies primarily in “treatment based on ZHENG differentiation.” From the view of data mining, ZHENG differentiation is modeled as a classification problem. In this paper, ML-kNN—a multilabel learning model—is used as the classification model for hypertension. Feature-level information fusion is also used for further utilization of all information. Experiment results show that ML-kNN can model the hypertension's ZHENG differentiation well. Information fusion helps improve models' performance

Understanding Structure of Poverty Dimensions in East Java: Bicluster Approach

Poverty is still become a main problem for Indonesia, where recently, the view point of poverty is not just from income or consumption, but it\u27s defined multidimensionally. The understanding of the structure of multidimensional poverty is essential to government to develop policies for poverty reduction. This paper aims to describe the structure of poverty in East Java by using variables forming the dimensions of poverty and to investigate any clustering patterns in the region of East Java with considering the poverty variables using biclustering method. Biclustering is an unsupervised technique in data mining where we are grouping scalars from the two-dimensional matrix. Using bicluster analysis, we found two bicluster where each bicluster has different characteristics.DOI: 10.15408/sjie.v6i2.476

A Computational Model of the Spread of Ancient Human Populations Based on Mitochondrial DNA Samples

The extraction of mitochondrial DNA (mtDNA) from ancient human population samples provides important data for the reconstruction of population influences, spread and evolution from the Neolithic to the present. This paper presents a mtDNA-based similarity measure between pairs of human populations and a computational model for the evolution of human populations. In a computational experiment, the paper studies the mtDNA information from five Neolithic and Bronze Age populations, namely the Andronovo, the Bell Beaker, the Minoan, the Rössen and the Únětice populations. In the past these populations were identified as separate cultural groups based on geographic location, age and the use of, decoration or shape of cultural artifacts