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At least 37 records · Page 2Linked to original sources
arXiv2007

Control of poultry chicken malaria by surface functionalized amorphous nanosilica

Surface modified amorphous nanoporous silica molecules with hydrophobic as well as hydrophilic character can be effectively used as therapeutic drug for combating chicken malaria in poultry industry. The amorphous nanosilica was developed by top-down approach using volcanic soil derived silica as source material. Amorphous silica has long been used as feed additive for poultry industry and considered to be safe for human consumption by WHO and USDA. The basic mechanism of action of these nanosilica molecules is mediated by the physical absorption of VLDL, serum triglycerides and other serum cholesterol components in the lipophilic nanopores of nanosilica. This reduces the supply of the host derived cholesterol, thus limiting the growth of the malarial parasite in vivo.

q-bio.BM↗
arXiv2007

Nanosilica mops up host lipids and fights baculovirus: a B. mori model

Malaria and other parasites, including virus often induce an increase in host lipids which the invaders use to their own advantage. We obtained encouraging results in our investigations on bird malaria with a new approach namely the use of nanosilica to mop up excess host lipids. While this project is continuing we have investigated another, simpler system namely silkworms which suffer from a deadly baculovirus, BmNPV. This virus decimates the infected population within 24 hours or so and no known antibiotic antidote or genetically resistant strain of silkworm3 exists. We report here a partial success, which is worth following up. Our rationale, we believe, has a broad and interdisciplinary appeal, for, this nanosilica treatment might be used together with other arsenals on all sorts of virus which take advantage of enhanced host lipids. It has not escaped our notice that Ebola and HIV also belong to this category. Nanoparticles are being preferentially harnessed, because they offer a greater surface area, circulate more easily and in lepidopteran system4 they are removed within 24 hours from the body. Lawry surmised, on cogent theoretical grounds that particles significantly smaller than micron order would be less harmful in the hemocoele. Furthermore, Hui-peng et al. pointed out that lipase treatment, the only viable option for controlling BmNPV interferes in hormonal balance and cannot be applied to pre molting stage.

q-bio.BM↗
arXiv2007

Nanosilica mop up host lipids and fights baculovirus

Various types of surface functionalized nanosilica (50-60 nm size with 3-10 nm inner pore size range) have been used to kill insect pests by sucking up cuticular lipids and breaking the water barrier. We have also utilized nanosilica for mopping up host lipids induced by the malarial parasite, P. gallinaceum in poultry birds; VLDL cholesterol and serum triglycerides are brought back to the normal level with a concomitant check in parasite growth. While this work continues, we have explored another more convenient system, silkworm (Bombyx mori) that is frequently decimated by a baculovirus, NPV for which no antidote is known so far. Here, too, viral infection enhances host lipids. Eight different types of nanosilica were injected in the virus infected silkworm (batches of 10 worms) after ensuring 100% survival up to cocoon formation in control larvae (injected with the same volume of ethanol, the medium of nanosilica). Of these 8, AL60102 and AL60106, have the most marked effect on infected silkworm, both as prophylactic and pharmaceutical agents. Normal larvae injected with these nanosilica survive up to cocoon formation.

q-bio.BM↗
arXiv2007

Control of rodent sleeping sickness disease by surface functionalized amorphous nanosilica

Wild animals, pets, zoo animals and mammals of veterinary importance heavily suffer from trypanosomiasis. Drugs with serious side effects are currently mainstay of therapies used by veterinarians. Trypanosomiasis is caused by Trypanosoma sp. leading to sleeping sickness in humans. Surface modified (hydrophobic and lipophilic) amorphous nanoporous silica molecules could be effectively used as therapeutic drug for combating trypanosomiasis. The amorphous nanosilica was developed by top-down approach using volcanic soil derived silica (Advasan; 50- 60 nm size with 3-10 nm inner pore size range) and diatomaceous earth (FS; 60-80 nm size with 3-5 nm inner pore size range) as source materials. According to WHO and USDA standards amorphous silica has long been used as feed additives for several veterinary industries and considered to be safe for human consumption. The basic mechanism of action of these nanosilica molecules is mediated by the physical absorption of HDL components in the lipophilic nanopores of nanosilica. This reduces the supply of the host derived cholesterol, thus limiting the growth of the Trypanosoma sp. in vivo.

q-bio.MN↗
arXiv2007

On Cycles in the Transcription Network of Saccharomyces cerevisiae

We investigate the cycles in the transcription network of S. cerevisiae. Unlike a similar network of E. coli, it contains many cycles. We characterize properties of these cycles and their place in the regulatory mechanism of the cell. Almost all cycles in the transcription network of S. cerevisiae are contained in a single strongly connected component, which we call LSCC (L for ``largest''), except for a single cycle of two transcription factors. Among different physiological conditions, cell cycle has the most significant relationship with LSCC, as the set of 64 transcription interactions that are active in all phases of the cell cycle has overlap of 27 with the interactions of LSCC (of which there are 49). Conversely, if we remove the interactions that are active in all phases of the cell cycle (fewer than 1% of the total), the LSCC would have only three nodes and 5 edges, 4 of which are active only in the stress response subnetwork. LSCC has a special place in the topology of the network and it can be used to define a natural hierarchy in the network; in every physiological subnetwork LSCC plays a pivotal role. Apart from those well-defined conditions, the transcription network of S. cerevisiae is devoid of cycles. It was observed that two conditions that were studied and that have no cycles of their own are exogenous: diauxic shift and DNA repair, while cell cycle, sporulation are endogenous.

q-bio.MN↗
arXiv2007

Transcription and noise in negative feedback loops

Recently, several studies have investigated the transcription process associated to specific genetic regulatory networks. In this work, we present a stochastic approach for analyzing the dynamics and effect of negative feedback loops (FBL) on the transcriptional noise. First, our analysis allows us to identify a bimodal activity depending of the strength of self-repression coupling D. In the strong coupling region D>>1, the variance of the transcriptional noise is found to be reduced a 28 % more than described earlier. Secondly, the contribution of the noise effect to the abundance of regulating protein becomes manifest when the coefficient of variation is computed. In the strong coupling region, this coefficient is found to be independent of all parameters and in fair agreement with the experimentally observed values. Finally, our analysis reveals that the regulating protein is significantly induced by the intrinsic and external noise in the strong coupling region. In short, it indicates that the existence of inherent noise in FBL makes it possible to produce a basal amount of proteins even though the repression level D is very strong.

q-bio.MN↗
arXiv2007

Ascorbic acid enhances the inhibitory effect of aspirin on neuronal cyclooxygenase-2-mediated prostaglandin E2 production

In the present study, we show that ascorbic acid dose-dependently inhibited interleukin-1beta (IL-1beta)-mediated PGE2 synthesis in the human neuronal cell line, SK-N-SH. Furthermore, in combination with aspirin, ascorbic acid augmented the inhibitory effect of aspirin on PGE2 synthesis. However, ascorbic acid had no synergistic effect along with other COX inhibitors (SC-58125 and indomethacin). The inhibition of IL-1beta-mediated PGE2 synthesis by ascorbic acid was not due to the inhibition of the expression of COX-2 or microsomal prostaglandin E synthase (mPGES-1). Rather, ascorbic acid dose-dependently (0.1-100 microM) produced a significant reduction in IL-1beta-mediated production of 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha), a reliable indicator of free radical formation, suggesting that the effects of ascorbic acid on COX-2-mediated PGE2 biosynthesis may be the result of the maintenance of the neuronal redox status since COX activity is known to be enhanced by oxidative stress. Our results provide in vitro evidence that the neuroprotective effects of ascorbic acid may depend, at least in part, on its ability to reduce neuronal COX-2 activity and PGE2 synthesis, owing to its antioxidant properties. Further, these experiments suggest that a combination of aspirin with ascorbic acid constitutes a novel approach to render COX-2 more sensitive to inhibition by aspirin, allowing an anti-inflammatory therapy with lower doses of aspirin, thereby avoiding the side effects of the usually high dose aspirin treatment.

q-bio.SC↗
arXiv2007

A Design of an Autonomous Molecule Loading/Transporting/Unloading System Using DNA Hybridization and Biomolecular Linear Motors

This paper describes a design of a molecular propagation system in molecular communication. Molecular communication is a new communication paradigm where biological and artificially-created nanomachines communicate over a short distance using molecules. A molecular propagation system in molecular communication directionally transports molecules from a sender to a receiver. In the design described in this paper, protein filaments glide over immobilized motor proteins along preconfigured microlithographic tracks, and the gliding protein filaments carry and transport molecules from a sender to a receiver. In the design, DNA hybridization is used to load and unload the molecules onto and from the carriers at a sender and a receiver. In the design, loading/transporting/unloading processes are autonomous and require no external control.

physics.bio-ph↗
arXiv2007

The p53-MDM2 network: from oscillations to apoptosis

The p53 protein is well-known for its tumour suppressor function. The p53-MDM2 negative feedback loop constitutes the core module of a network of regulatory interactions activated under cellular stress. In normal cells, the level of p53 proteins is kept low by MDM2, i.e. MDM2 negatively regulates the activity of p53. In the case of DNA damage,the p53-mediated pathways are activated leading to cell cycle arrest and repair of the DNA. If repair is not possible due to excessive damage, the p53-mediated apoptotic pathway is activated bringing about cell death. In this paper, we give an overview of our studies on the p53-MDM2 module and the associated pathways from a systems biology perspective. We discuss a number of key predictions, related to some specific aspects of cell cycle arrest and cell death, which could be tested in experiments.

q-bio.MN↗
arXiv2007

Differential and graphical approaches to multistability theory for chemical reaction networks

The use of mathematical models has helped to shed light on countless phenomena in chemistry and biology. Often, though, one finds that systems of interest in these fields are dauntingly complex. In this paper, we attempt to synthesize and expand upon the body of mathematical results pertaining to the theory of multiple equilibria in chemical reaction networks (CRNs), which has yielded surprising insights with minimal computational effort. Our central focus is a recent, cycle-based theorem by Gheorghe Craciun and Martin Feinberg, which is of significant interest in its own right and also serves, in a somewhat restated form, as the basis for a number of fruitful connections among related results.

q-bio.MN↗
arXiv2007

Cancer Genesis and Progression as Dynamics in Functional Landscape of Endogenous Molecular-Cellular Network

An endogenous molecular-cellular network for both normal and abnormal functions is assumed to exist. This endogenous network forms a nonlinear stochastic dynamical system, with many stable attractors in its functional landscape. Normal or abnormal robust states can be decided by this network in a manner similar to the neural network. In this context cancer is hypothesized as one of its robust intrinsic states. This hypothesis implies that a nonlinear stochastic mathematical cancer model is constructible based on available experimental data and its quantitative prediction is directly testable. Within such model the genesis and progression of cancer may be viewed as stochastic transitions between different attractors. Thus it further suggests that progressions are not arbitrary. Other important issues on cancer, such as genetic vs epigenetics, double-edge effect, dormancy, are discussed in the light of present hypothesis. A different set of strategies for cancer prevention, cure, and care, is therefore suggested.

q-bio.SC↗
arXiv2007

Modular co-evolution of metabolic networks

The architecture of biological networks has been reported to exhibit high level of modularity, and to some extent, topological modules of networks overlap with known functional modules. However, how the modular topology of the molecular network affects the evolution of its member proteins remains unclear. In this work, the functional and evolutionary modularity of Homo sapiens (H. sapiens) metabolic network were investigated from a topological point of view. Network decomposition shows that the metabolic network is organized in a highly modular core-periphery way, in which the core modules are tightly linked together and perform basic metabolism functions, whereas the periphery modules only interact with few modules and accomplish relatively independent and specialized functions. Moreover, over half of the modules exhibit co-evolutionary feature and belong to specific evolutionary ages. Peripheral modules tend to evolve more cohesively and faster than core modules do. The correlation between functional, evolutionary and topological modularity suggests that the evolutionary history and functional requirements of metabolic systems have been imprinted in the architecture of metabolic networks. Such systems level analysis could demonstrate how the evolution of genes may be placed in a genome-scale network context, giving a novel perspective on molecular evolution.

q-bio.MN↗
arXiv2007

Estimating the size of the solution space of metabolic networks

In this work we propose a novel algorithmic strategy that allows for an efficient characterization of the whole set of stable fluxes compatible with the metabolic constraints. The algorithm, based on the well-known Bethe approximation, allows the computation in polynomial time of the volume of a non full-dimensional convex polytope in high dimensions. The result of our algorithm match closely the prediction of Monte Carlo based estimations of the flux distributions of the Red Blood Cell metabolic network but in incomparably shorter time. We also analyze the statistical properties of the average fluxes of the reactions in the E-Coli metabolic network and finally to test the effect of gene knock-outs on the size of the solution space of the E-Coli central metabolism.

cond-mat.dis-nn↗
arXiv2007

Pseudo-Random Fluctuations, Stochastic Cooperativity and Burstiness in Dynamically Unstable High-Dimensional Biochemical Networks

The goal of this paper is to outline a scenario of emerging stochasticity in high-dimensional highly nonlinear systems, such as genetic regulatory networks (GRN). We focus attention on the fact that in such systems confluence of all the factors necessary for gene expression is a comparatively rare event, and only massive redundancy makes such events sufficiently frequent. An immediate consequence of this rareness is burstiness in mRNA and protein copy numbers, a well known experimentally observed effect. We introduce the concept of stochastic cooperativity and show that this phenomenon is a natural consequence of high dimensionality coupled with highly nonlinearity of a dynamical system. In mathematical terms, burstiness is associated with heavy-tailed probability distributions of stochastic processes describing the dynamics of the system. The sequence of stochastic cooperativity events allows for transition from continuous deterministic dynamics expressed in terms of ordinary differential equations (ODE) to discrete stochastic dynamics expressed in terms of Langevin and Fokker-Plank equations. We demonstrate also that high-dimensional nonlinear systems, even in the absence of explicit mechanisms for suppressing inherent instability, may nevertheless reside in a state of stationary pseudo-random fluctuations which for all practical purposes may be regarded as stochastic process. This type of stochastic behavior is an inherent property of such systems and requires neither an external random force, nor highly specialized conditions of bistability.

q-bio.MN↗
arXiv2007

Two distinct logical types of network control in gene expression profiles

In unicellular organisms such as bacteria the same acquired mutations beneficial in one environment can be restrictive in another. However, evolving Escherichia coli populations demonstrate remarkable flexibility in adaptation. The mechanisms sustaining genetic flexibility remain unclear. In E. coli the transcriptional regulation of gene expression involves both dedicated regulators binding specific DNA sites with high affinity and also global regulators - abundant DNA architectural proteins of the bacterial chromoid binding multiple low affinity sites and thus modulating the superhelical density of DNA. The first form of transcriptional regulation is dominantly pairwise and specific, representing digitial control, while the second form is (in strength and distribution) continuous, representing analog control. Here we look at the properties of effective networks derived from significant gene expression changes under variation of the two forms of control and find that upon limitations of one type of control (caused e.g. by mutation of a global DNA architectural factor) the other type can compensate for compromised regulation. Mutations of global regulators significantly enhance the digital control; in the presence of global DNA architectural proteins regulation is mostly of the analog type, coupling spatially neighboring genomic loci; together our data suggest that two logically distinct types of control are balancing each other. By revealing two distinct logical types of control, our approach provides basic insights into both the organizational principles of transcriptional regulation and the mechanisms buffering genetic flexibility. We anticipate that the general concept of distinguishing logical types of control will apply to many complex biological networks.

q-bio.GN↗
arXiv2007

Prediction and verification of indirect interactions in densely interconnected regulatory networks

We develop a matrix-based approach to predict and verify indirect interactions in gene and protein regulatory networks. It is based on the approximate transitivity of indirect regulations (e.g. A regulates B and B regulates C often implies that A regulates C) and optimally takes into account the length of a cascade and signs of intermediate interactions. Our method is at its most powerful when applied to large and densely interconnected networks. It successfully predicts both the yet unknown indirect regulations, as well as the sign (activation or repression) of already known ones. The reliability of sign predictions was calibrated using the gold-standard sets of positive and negative interactions. We fine-tuned the parameters of our algorithm by maximizing the area under the Receiver Operating Characteristic (ROC) curve. We then applied the optimized algorithm to large literature-derived networks of all direct and indirect regulatory interactions in several model organisms (Homo sapiens, Saccharomyces cerevisiae, Arabidopsis thaliana and Drosophila melanogaster).

q-bio.QM↗