Rescuing the Function of Mutated Isocitrate Dehydrogenase

Isocitrate dehydrogenase (IDH1), an enzyme involved in the conversion of isocitrate into α-ketoglutarate, is an important enzyme in the citric acid cycle—a primary source of energy for the human body. A mutation in IDH1 disrupts its structure and overall functionality, leading to the high probability of developing aggressive brain tumors. In order to assess and repair this impairment, two synthetic binders, or FABs, were used to determine the effect on the activity of mutant IDH1. Comparison of the activities of these two different FABs revealed to what degree the activity of this enzyme was restored. The wild-type activity for IDH1 is greater than the activity of the mutant enzyme without the presence of any FABs. With the presence of FAB4, the activity was increased a significant degree. In comparison, FAB5 exhibits an opposite effect on the activity of the enzyme, lowering the enzyme’s activity considerably. FAB4 helped to bring the activity of mutated IDH1 closer to that of wild-type IDH1; from this result, it’s possible that FAB4 has the potential to lead to the development of a potential therapeutic agent.Indiana University South Bend Department of Chemistry and Biochemistr

Abnormal Segregation of Alleles and Haplotypes at the Polymorphic Site of the PRNP Gene Within Promoter and Intron 1 Regions in Polish Holstein–Friesian Cattle

Allele and haplotype segregation at the polymorphic sites within the promoter (23indel) and intron 1 (12indel) regions of the PRNP gene was analyzed in Polish Holstein–Friesian cattle. More 23del/del homozygotes and fewer 23ins/ins homozygotes than expected were observed in the offspring of ♂ 23ins/del × ♀ 23ins/del parents. In the offspring of ♂ 23ins/del × ♀ 23del/del parents and ♂ 23del/del × ♀ 23ins/del parents, a trend toward more 23del/del animals and fewer 23ins/del animals than expected was noted. At the 12indel polymorphic site, the only trend found was one toward fewer 12ins/ins genotypes and more 12ins/del and 12del/del genotypes than expected in the offspring of ♂ 12ins/del × ♀ 12ins/del parents. An analysis of haplotype segregation revealed more 23del-12del/23del-12del diplotypes and fewer 23ins-12ins/23ins-12ins diplotypes at the significance threshold than expected in the offspring of ♂ 23ins-12ins/23del-12del × ♀ 23ins-12ins/23del-12del parents

Simulation methods for spatiotemporal models of biochemical signaling networks

Cells use signaling networks consisting of multiple interacting proteins to respond to changes in their environment. In many situations, such as chemotaxis, spatial and temporal information must be transmitted through a signaling network. Recent computational studies have emphasized the importance of cellular geometry in signal transduction, but have been limited in their ability to accurately represent complex cell morphologies. We present a finite volume method that addresses this problem. Our method uses Cartesian cut cells in a differential algebraic formulation to handle the complex boundary dynamics encountered in biological systems. The method is second order in space and time. Several models of signaling systems are simulated in realistic cell morphologies obtained from live cell images. We then examine the effects of geometry on signal transduction. External signals can trigger cells to polarize and move in a specific direction. During migration, spatially localized activity of proteins is maintained. To investigate the effects of morphological changes on intracellular signaling, we present a numerical scheme consisting of a cut cell finite volume spatial discretization coupled with level set methods to simulate the resulting advection-reaction-diffusion equation. We then show that shape deformations drive a Turing-type system into an unstable regime. The method is also applied to a model of a signaling network in a migrating fibroblast. Determining the signaling mechanisms used by membrane proteins that interact with the cytoskeleton is important for understanding phenomena such as T-cell activation and viral infection. To investigate these interactions, recent experiments have tracked the movements of single lipids and glycosyl-phosphatidylinositol (GPI) anchored protein clusters tagged with 40 nm gold particles. These experiments reveal regions of transient confinement and transient anchorage of the particles. The distribution of transient anchorage release times exhibits a long tail. We developed a stochastic model of the system to explain the transient anchorage release times and the underlying biochemical reaction system

A cut-cell method for simulating spatial models of biochemical reaction networks in arbitrary geometries

Cells use signaling networks consisting of multiple interacting proteins to respond to changes in their environment. In many situations, such as chemotaxis, spatial and temporal information must be transmitted through the network. Recent computational studies have emphasized the importance of cellular geometry in signal transduction, but have been limited in their ability to accurately represent complex cell morphologies. We present a finite volume method that addresses this problem. Our method uses Cartesian cut cells and is second order in space and time. We use our method to simulate several models of signaling systems in realistic cell morphologies obtained from live cell images and examine the effects of geometry on signal transduction

The effect of silkworm pupae and mealworm larvae meals as dietary protein components on performance indicators in rabbits

El objetivo de este estudio es evaluar el efecto de la alimentación de conejos con harinas de pupas de gusanos de seda y larvas de gusanos de la harina sobre sus indicadores de rendimiento. Se dividieron noventa (90) conejos en tres grupos. El grupo testigo (T) fue alimentado con un 10% de harina de soya (HS), el grupo HS recibió una dieta que incluía un 5% de HS y un 4% de harina de pupas de gusanos de seda, y el grupo HLGH recibió una dieta que incluía un 5% de HS y un 4% de harina de larvas de gusanos de seda. Se determinó el peso corporal de los conejos y la ganancia media diaria. Se calculó el índice de conversión alimenticia (ICA). Al final del periodo de engorde, los animales fueron sometidos a eutanasia, desollados y eviscerados para determinar las características de sus canales. Se recogieron los músculos del pernil y del lomo para analizar la composición química. Al final del período de engorde, los conejos de los grupos HS y HLGH eran más pesados que los conejos T (2.606,5 y 2.584,8 frente a 2.404,0 g), lo que también mejoró las características generales de la canal, mientras que el ICA fue similar en los diversos grupos. Sin embargo, el alimentar a los conejos con harinas adicionadas con insectos aumentó la cantidad de extracto etéreo en sus músculos. Con base en los resultados obtenidos, se puede concluir que en las dietas de los conejos se puede sustituir parcialmente la harina de soya con las harinas de pupas de gusanos de seda y de larvas de gusanos de harina.This study aimed to evaluate the effect of feeding rabbits with silkworm pupae and mealworm larvae meals on their performance indicators. Ninety (90) rabbits were divided into three groups. Control group (C) was fed with 10% soybean meal (SBM), SPM group received the diet including 5 % SBM and 4 % of silkworm pupae meal, and MLM group received the diet including 5 % SBM and 4 % of mealworm larvae meal. The body weight of rabbits and average daily gains were determined. Feed conversion ratio (FCR) was calculated. At the end of fattening period, the animals were euthanized, skinned and eviscerated to determine their carcasses characteristic. Hind leg and loin muscles were collected for analyses of the chemical composition. At the end of fattening period, rabbits from groups SPM and MLM were heavier than C rabbits (2,606.5 and 2,584.8 vs 2,404.0 g), which also improved their overall carcass characteristic while FCR was similar between groups. However, feeding rabbits with the addition of insect's meals increased the amount of ether extract in their muscles. Based on the results obtained, it may be concluded that SBM may be partially replaced by silkworm pupae and mealworm larvae meals in rabbit diets

Simulating Biochemical Signaling Networks in Complex Moving Geometries

Signaling networks regulate cellular responses to environmental stimuli through cascades of protein interactions. External signals can trigger cells to polarize and move in a specific direction. During migration, spatially localized activity of proteins is maintained. To investigate the effects of morphological changes on intracellular signaling, we developed a numerical scheme consisting of a cut cell finite volume spatial discretization coupled with level set methods to simulate the resulting advection-reaction-diffusion system. We then apply the method to several biochemical reaction networks in changing geometries. We found that a Turing instability can develop exclusively by cell deformations that maintain constant area. For a Turing system with a geometry-dependent single or double peak solution, simulations in a dynamically changing geometry suggest that a single peak solution is the only stable one, independent of the oscillation frequency. The method is also applied to a model of a signaling network in a migrating fibroblast

Volunteer Computing Simulation Using Repast And Mason

Volunteer environments usually consist of a large number of computing nodes,with highly dynamic characteristics, therefore reliable models for a planning ofthe whole computing are highly desired. An easy to implement approach to mo-delling and simulation of such environments may employ agent-based universalsimulation frameworks, such as RePast or MASON. In the course of the paperthe above-mentioned simulation frameworks are adapted to support simulationof volunteer computing. After giving implementation details, selected resultsconcerning computing time and speedup are given and are compared with theones obtained from an actual volunteer environment

Reception Tests of the Cryogenic Distribution line for the Large Hadron Collider

The paper describes the thermo-mechanical validation of the first sector of cryogenic distribution line (QRL) [1]. The design of the line is recalled and the test methodology presented together with the main results of the reception test at cryogenic temperature