Topoisomerase II– and Condensin-Dependent Breakage of MEC1ATR-Sensitive Fragile Sites Occurs Independently of Spindle Tension,Anaphase, or Cytokinesis

Fragile sites are loci of recurrent chromosome breakage in the genome. They are found in organisms ranging from bacteria to humans and are implicated in genome instability, evolution, and cancer. In budding yeast, inactivation of Mec1, a homolog of mammalian ATR, leads to chromosome breakage at fragile sites referred to as replication slow zones (RSZs). RSZs are proposed to be homologous to mammalian common fragile sites (CFSs) whose stability is regulated by ATR. Perturbation during S phase, leading to elevated levels of stalled replication forks, is necessary but not sufficient for chromosome breakage at RSZs or CFSs. To address the nature of additional event(s) required for the break formation, we examined involvement of the currently known or implicated mechanisms of endogenous chromosome breakage, including errors in replication fork restart, premature mitotic chromosome condensation, spindle tension, anaphase, and cytokinesis. Results revealed that chromosome breakage at RSZs is independent of the RAD52 epistasis group genes and of TOP3, SGS1, SRS2, MMS4, or MUS81, indicating that homologous recombination and other recombination-related processes associated with replication fork restart are unlikely to be involved. We also found spindle force, anaphase, or cytokinesis to be dispensable. RSZ breakage, however, required genes encoding condensin subunits (YCG1, YSC4) and topoisomerase II (TOP2). We propose that chromosome break formation at RSZs following Mec1 inactivation, a model for mammalian fragile site breakage, is mediated by internal chromosomal stress generated during mitotic chromosome condensation.     

Accurate intraocular pressure prediction from applanation response data using genetic algorithm and neural networks

The fact that Goldmann applanation tonometry does not accurately account for individual corneal elastic stiffness often leads to inaccuracy in the measurement of intraocular pressure (IOP). IOP should account not only for the effect of central corneal thickness (CCT) but should also account for other corneal biomechanical factors. A computational method for accurate and reliable determination of IOP is investigated with a modified applanation tonometer in this paper. The proposed method uses a combined genetic algorithm/neural network procedure to match the clinically measured applanation force-displacement history with that obtained from a nonlinear finite element simulation of applanation. An additional advantage of the proposed method is that it also provides the ability to determine CCT and material properties of the cornea from the same applanation response data. The performance of the proposed method has been demonstrated through a parametric study and via comparison with a well known clinical case. The proposed method is also shown to be computationally efficient, which is an important practical consideration for clinical application.     

Pegasys: software for executing and integrating analyses of biological sequences

Background  

We present Pegasys – a flexible, modular and customizable software system that facilitates the execution and data integration from heterogeneous biological sequence analysis tools.     

First report of Phytopythium vexans causing the “Avocado sadness” in Michoacan,Mexico

Mexico is the main producer, consumer and exporter of avocado in the world, being Michoacan the main producer state contributing more than 80% of the national production. There are phytopathogens that decimate the production causing the death of the tree. Root samples were collected in avocado trees that showed the characteristic symptomatology of the disease known as avocado sadness, the sampling was carried out in four of the main avocado producing towns, in the state of Michoacan, Mexico. The isolation consisted in sowing root tissue in Petri dishes with V8^®-PARPH culture medium, subsequently they were identified morphologically and for species level it was determined by molecular biology, with the PCR-ITS technique. Pathogenicity tests were performed in triplicate with avocado seedlings with more than six leaves. After 24 hours, the inoculated plants expressed decay in the apical part, after 120 hours the leaves showed yellowing and after 15 days there was a generalized wilt on the stem and leaves, re-isolating the phytopathogen Phytopythium vexans. This study confirms the first report of the oomycete P. vexans affecting avocado trees in the most important producing region of the Mexican Republic.     

Effect of cornea material stiffness on measured intraocular pressure

Intraocular pressure (IOP) in the human eye as measured by a Goldmann applanation tonometer (GAT) is known to be affected by individual differences in central corneal thickness (CCT). However, data from clinical studies also show considerable scatter in the correlation between measured IOP and CCT. One possible implication of the large observed scatter is that the true IOP (IOPT) also depends significantly on individual variations in the material stiffness properties of the cornea. This hypothesis is explored and evaluated herein using computational simulation of applanation tonometry. A simplified 2D finite element model of the eye, which employs a calibrated nonlinear transversely isotropic material model for the cornea, is developed, and a series of GAT simulations is carried out to study the effect of geometry and material properties of the cornea on the IOP readings obtained via GAT. The results of this parametric study provide a simple correction equation, which quantifies the effect on measured IOP of variations in CCT and corneal material stiffness. In addition, several previously proposed IOP correction equations are compared with the one proposed here.     

Inverse folding of RNA pseudoknot structures

Background  

RNA exhibits a variety of structural configurations. Here we consider a structure to be tantamount to the noncrossing Watson-Crick and G-U-base pairings (secondary structure) and additional cross-serial base pairs. These interactions are called pseudoknots and are observed across the whole spectrum of RNA functionalities. In the context of studying natural RNA structures, searching for new ribozymes and designing artificial RNA, it is of interest to find RNA sequences folding into a specific structure and to analyze their induced neutral networks. Since the established inverse folding algorithms, RNAinverse, RNA-SSD as well as INFO-RNA are limited to RNA secondary structures, we present in this paper the inverse folding algorithm Inv which can deal with 3-noncrossing, canonical pseudoknot structures.