Gene Expression changes in aging zebrafish (Danio rerio) brains are sexually dimorphic

Cataloged from PDF version of article.Background: Brain aging is a multi-factorial process due to both genetic and environmental factors. The zebrafish has recently become a popular model organism for examining aging and age-related diseases because as in humans they age gradually and exhibit cognitive decline. Few studies have examined the biological changes in the aging brain that may contribute to these declines and none have examined them within individuals with respect to gender. Our aim was to identify the main genetic pathways associated with zebrafish brain aging across gender. We chose males and females from specific age groups (young, 7.5-8.5 months and old, 31-36 months) based on the progression of cognitive decline in zebrafish. RNA was isolated from individual brains and subjected to microarray and qPCR analysis. Statistical analyses were performed using a two-way ANOVA and the relevant post-hoc tests. Results: Our results demonstrated that in the brains of young and old male and female zebrafish there were over 500 differentially expressed genes associated with multiple pathways but most notably were those related to neurogenesis and cell differentiation, as well as brain and nervous system development. Conclusions: The gene expression of multiple pathways is altered with age and differentially expressed in males and females. Future studies will be aimed at determining the causal relationships of age-related changes in gene expression in individual male and female brains, as well as possible interventions that counteract these alterations

Nonlinearities and Parametric Amplification in Superconducting Coplanar Waveguide Resonators

Experimental investigations of the nonlinear properties of superconducting niobium coplanar waveguide resonators are reported. The nonlinearity due to a current dependent kinetic inductance of the center conductor is strong enough to realize bifurcation of the nonlinear oscillator. When driven with two frequencies near the threshold for bifurcation, parametric amplification with a gain of +22.4 dB is observed.Comment: 4 pages, 5 figures, 1 table. In version 2: Added appendix with model description and fits to measurements. Minor corrections and rephrasin

Senescence and immortality in hepatocellular carcinoma

Cataloged from PDF version of article.Cellular senescence is a process leading to terminal growth arrest with characteristic morphological features. This process is mediated by telomere-dependent, oncogene-induced and ROS-induced pathways, but persistent DNA damage is the most common cause. Senescence arrest is mediated by p16(INK4a)- and p21(Cip1)-dependent pathways both leading to retinoblastoma protein (pRb) activation. p53 plays a relay role between DNA damage sensing and p21(Cip1) activation. pRb arrests the cell cycle by recruiting proliferation genes to facultative heterochromatin for permanent silencing. Replicative senescence that occurs in hepatocytes in culture and in liver cirrhosis is associated with lack of telomerase activity and results in telomere shortening. Hepatocellular carcinoma (HCC) cells display inactivating mutations of p53 and epigenetic silencing of p16(INK4a). Moreover, they re-express telomerase reverse transcriptase required for telomere maintenance. Thus, senescence bypass and cellular immortality is likely to contribute significantly to HCC development. Oncogene-induced senescence in premalignant lesions and reversible immortality of cancer cells including HCC offer new potentials for tumor prevention and treatment. (C) 2008 Elsevier Ireland Ltd. All rights reserved

A Novel Broadband Multilevel Fast Multipole Algorithm with Incomplete-Leaf Tree Structures for Multiscale Electromagnetic Problems

An efficient and versatile broadband multilevel fast multipole algorithm (MLFMA), which is capable of handling large multiscale electromagnetic problems with a wide dynamic range of mesh sizes, is presented. By invoking a novel concept of incomplete-leaf tree structures, where only the overcrowded boxes are divided into smaller ones for a given population threshold, versatility of using variable-sized boxes is achieved. Consequently, for geometries containing highly overmeshed local regions, the proposed method is always more efficient than the conventional MLFMA for the same accuracy, while it is always more accurate if the efficiency is comparable. Furthermore, in such a population-based clustering scenario, the error is controllable regardless of the number of levels. Several canonical examples are provided to demonstrate the superior efficiency and accuracy of the proposed algorithm in comparison with the conventional MLFMA. � 2016 IEEE

Incomplete-Leaf Multilevel Fast Multipole Algorithm for Multiscale Penetrable Objects Formulated with Volume Integral Equations

Recently introduced incomplete-leaf (IL) tree structures for multilevel fast multipole algorithm (referred to as IL-MLFMA) is proposed for the analysis of multiscale inhomogeneous penetrable objects, in which there are multiple orders of magnitude differences among the mesh sizes. Considering a maximum Schaubert-Wilton-Glisson function population threshold per box, only overcrowded boxes are recursively divided into proper smaller boxes, leading to IL tree structures consisting of variable box sizes. Such an approach: 1) significantly reduces the CPU time for near-field calculations regarding overcrowded boxes, resulting a superior efficiency in comparison with the conventional MLFMA where fixed-size boxes are used and 2) effectively reduces the computational error of the conventional MLFMA for multiscale problems, where the protrusion of the basis/testing functions from their respective boxes dramatically impairs the validity of the addition theorem. Moreover, because IL-MLFMA is able to use deep levels safely and without compromising the accuracy, the memory consumption is significantly reduced compared with that of the conventional MLFMA. Several examples are provided to assess the accuracy and the efficiency of IL-MLFMA for multiscale penetrable objects. © 2017 IEEE

Broadband multilevel fast multipole algorithm for large-scale problems with nonuniform discretizations

We present a broadband implementation of the multilevel fast multipole algorithm (MLFMA) for fast and accurate solutions of multiscale problems involving highly nonuniform discretizations. Incomplete tree structures, which are based on population-based clustering with flexible leaf-level boxes at different levels, are used to handle extremely varying triangulation sizes on the same structures. Superior efficiency and accuracy of the developed implementation, in comparison to the standard and broadband MLFMA solvers employing conventional tree structures, are demonstrated on practical problems. © 2016 IEEE

Genome-Wide Transcriptional Reorganization Associated with Senescence-to-Immortality Switch during Human Hepatocellular Carcinogenesis

Cataloged from PDF version of article.Senescence is a permanent proliferation arrest in response to cell stress such as DNA damage. It contributes strongly to tissue aging and serves as a major barrier against tumor development. Most tumor cells are believed to bypass the senescence barrier (become "immortal") by inactivating growth control genes such as TP53 and CDKN2A. They also reactivate telomerase reverse transcriptase. Senescence-to-immortality transition is accompanied by major phenotypic and biochemical changes mediated by genome-wide transcriptional modifications. This appears to happen during hepatocellular carcinoma (HCC) development in patients with liver cirrhosis, however, the accompanying transcriptional changes are virtually unknown. We investigated genome-wide transcriptional changes related to the senescence-to-immortality switch during hepatocellular carcinogenesis. Initially, we performed transcriptome analysis of senescent and immortal clones of Huh7 HCC cell line, and identified genes with significant differential expression to establish a senescence-related gene list. Through the analysis of senescence-related gene expression in different liver tissues we showed that cirrhosis and HCC display expression patterns compatible with senescent and immortal phenotypes, respectively; dysplasia being a transitional state. Gene set enrichment analysis revealed that cirrhosis/senescence-associated genes were preferentially expressed in non-tumor tissues, less malignant tumors, and differentiated or senescent cells. In contrast, HCC/immortality genes were up-regulated in tumor tissues, or more malignant tumors and progenitor cells. In HCC tumors and immortal cells genes involved in DNA repair, cell cycle, telomere extension and branched chain amino acid metabolism were up-regulated, whereas genes involved in cell signaling, as well as in drug, lipid, retinoid and glycolytic metabolism were down-regulated. Based on these distinctive gene expression features we developed a 15-gene hepatocellular immortality signature test that discriminated HCC from cirrhosis with high accuracy. Our findings demonstrate that senescence bypass plays a central role in hepatocellular carcinogenesis engendering systematic changes in the transcription of genes regulating DNA repair, proliferation, differentiation and metabolism