Spatial Fluctuations and the Flipping of the Genetic Switch in a Cellular System

2000 ◽  
Vol 651 ◽  
Author(s):  
Ralf Metzler

Abstract– It has been realised that noise plays an important rôle in cellular processes where fluctuation induced number fluctuations of certain messenger molecules become non–negligible, due to the small total number of these molecules within one cell. In the following, it is argued that spatial fluctuations of such molecules and their impact on genetic switches should be considered as well.

2018 ◽  
Vol 4 (4) ◽  
pp. 24 ◽  
Author(s):  
Gabriela Chavez-Calvillo ◽  
Sarah Martin ◽  
Chad Hamm ◽  
Joanna Sztuba-Solinska

Advances in next-generation sequencing have facilitated the discovery of a multitude of long non-coding RNAs (lncRNAs) with pleiotropic functions in cellular processes, disease, and viral pathogenesis. It came as no surprise when viruses were also revealed to transcribe their own lncRNAs. Among them, gammaherpesviruses, one of the three subfamilies of the Herpesviridae, code their largest number. These structurally and functionally intricate non-coding (nc) transcripts modulate cellular and viral gene expression to maintain viral latency or prompt lytic reactivation. These lncRNAs allow for the virus to escape cytosolic surveillance, sequester, and re-localize essential cellular factors and modulate the cell cycle and proliferation. Some viral lncRNAs act as “messenger molecules”, transferring information about viral infection to neighboring cells. This broad range of lncRNA functions is achieved through lncRNA structure-mediated interactions with effector molecules of viral and host origin, including other RNAs, proteins and DNAs. In this review, we discuss examples of gammaherpesvirus-encoded lncRNAs, emphasize their unique structural attributes, and link them to viral life cycle, pathogenesis, and disease progression. We will address their potential as novel targets for drug discovery and propose future directions to explore lncRNA structure and function relationship.


Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2174 ◽  
Author(s):  
Meysam Sarshar ◽  
Daniela Scribano ◽  
Cecilia Ambrosi ◽  
Anna Teresa Palamara ◽  
Andrea Masotti

Over the past decade, short non-coding microRNAs (miRNAs), including circulating and fecal miRNAs have emerged as important modulators of various cellular processes by regulating the expression of target genes. Recent studies revealed the role of miRNAs as powerful biomarkers in disease diagnosis and for the development of innovative therapeutic applications in several human conditions, including intestinal diseases. In this review, we explored the literature and summarized the role of identified dysregulated fecal miRNAs in intestinal diseases, with particular focus on colorectal cancer (CRC) and celiac disease (CD). The aim of this review is to highlight one fascinating aspect of fecal miRNA function related to gut microbiota shaping and bacterial metabolism influencing. The role of miRNAs as “messenger” molecules for inter kingdom communications will be analyzed to highlight their role in the complex host-bacteria interactions. Moreover, whether fecal miRNAs could open up new perspectives to develop novel suitable biomarkers for disease detection and innovative therapeutic approaches to restore microbiota balance will be discussed.


2021 ◽  
Vol 12 ◽  
Author(s):  
Ritesh K Shukla ◽  
Ashish Badiye ◽  
Kamayani Vajpayee ◽  
Neeti Kapoor

The rapid advancement of nanotechnology enhances the production of different nanoparticles that meet the demand of various fields like biomedical sciences, industrial, material sciences and biotechnology, etc. This technological development increases the chances of nanoparticles exposure to human beings, which can threaten their health. It is well known that various cellular processes (transcription, translation, and replication during cell proliferation, cell cycle, cell differentiation) in which genetic materials (DNA and RNA) are involved play a vital role to maintain any structural and functional modification into it. When nanoparticles come into the vicinity of the cellular system, chances of uptake become high due to their small size. This cellular uptake of nanoparticles enhances its interaction with DNA, leading to structural and functional modification (DNA damage/repair, DNA methylation) into the DNA. These modifications exhibit adverse effects on the cellular system, consequently showing its inadvertent effect on human health. Therefore, in the present study, an attempt has been made to elucidate the genotoxic mechanism of nanoparticles in the context of structural and functional modifications of DNA.


2016 ◽  
Author(s):  
M. Leon ◽  
M. L. Woods ◽  
A.J.H. Fedorec ◽  
C.P. Barnes

AbstractGenetic switches exhibit multistability, form the basis of epigenetic memory, and are found in natural decision making systems, such as cell fate determination in developmental pathways. Synthetic genetic switches can be used for recording the presence of different environmental signals, for changing phenotype using synthetic inputs and as building blocks for higher-level sequential logic circuits. Understanding how multistable switches can be constructed and how they function within larger biological systems is therefore key to synthetic biology. Here we present a new computational tool, called StabilityFinder, that takes advantage of sequential Monte Carlo methods to identify regions of parameter space capable of producing multistable behaviour, while handling uncertainty in biochemical rate constants and initial conditions. The algorithm works by clustering trajectories in phase space, and iteratively minimizing a distance metric. Here we examine a collection of models of genetic switches, ranging from the deterministic Gardner toggle switch to stochastic models containing different positive feedback connections. We uncover the design principles behind making bistable, tristable and quadristable switches, and find that rate of gene expression is a key parameter. We demonstrate the ability of the framework to examine more complex systems and examine the design principles of a three gene switch. Our framework allows us to relax the assumptions that are often used in genetic switch models and we show that more complex abstractions are still capable of multistable behaviour. Our results suggest many ways in which genetic switches can be enhanced and offer designs for the construction of novel switches. Our analysis also highlights subtle changes in correlation of experimentally tunable parameters that can lead to bifurcations in deterministic and stochastic systems. Overall we demonstrate that StabilityFinder will be a valuable tool in the future design and construction of novel gene networks.


Author(s):  
Gabriela Chavez Calvillo ◽  
Sarah Martin ◽  
Chad Hamm ◽  
Joanna Sztuba-Solinska

Advances in next-generation sequencing have facilitated the discovery of a multitude of long non-coding RNAs (lncRNAs) with pleiotropic functions in cellular processes, disease and viral pathogenesis. It came as no surprise when viruses were also revealed to transcribe their own lncRNAs. Among them, gammaherpesviruses, one of the three subfamilies of the Herpesviridae, code their largest number. These structurally and functionally intricate non-coding (nc) transcripts modulate cellular and viral gene expression to maintain viral latency or prompt lytic reactivation. The lncRNAs allow the virus to escape cytosolic surveillance, sequester and re-localize essential cellular factors and modulate the cell cycle and proliferation. Some viral lncRNAs act as “messenger molecules”, transferring information about viral infection to neighboring cells. This broad range of lncRNA functions is achieved through lncRNA structure-mediated interactions with effector molecules of viral and host origin, including other RNAs, proteins and DNAs. In this review, we discuss examples of gammaherpesvirus-encoded lncRNAs, emphasize their unique structural attributes, and link them to viral life cycle, pathogenesis and disease progression. We will address their potential as novel targets for drug discovery and propose future directions to explore lncRNA structure and function relationship.


Author(s):  
M.A. Cuadros ◽  
M.J. Martinez-Guerrero ◽  
A. Rios

In the chick embryo retina (days 3-4 of incubation), coinciding with an increase in cell death, specialized phagocytes characterized by intense acid phosphatase activity have been described. In these preparations, all free cells in the vitreal humor (vitreal cells) were strongly labeled. Conventional TEM and SEM techniques were used to characterize them and attempt to determine their relationship with retinal phagocytes.Two types of vitreal cells were distinguished. The first are located at some distance from the basement membrane of the neuroepithelium, and are rounded, with numerous vacuoles and thin cytoplasmic prolongations. Images of exo- and or endocytosis were frequent; the cells showed a well-developed Golgi apparatus (Fig. 1) In SEM images, the cells was covered with short cellular processes (Fig. 3). Cells lying parallel to or alongside the basement membrane are elongated. The plasma membrane is frequently in intimate contact with the basement membrane. These cells have generally a large cytoplasmic expansion (Fig. 5).


2005 ◽  
Vol 41 ◽  
pp. 15-30 ◽  
Author(s):  
Helen C. Ardley ◽  
Philip A. Robinson

The selectivity of the ubiquitin–26 S proteasome system (UPS) for a particular substrate protein relies on the interaction between a ubiquitin-conjugating enzyme (E2, of which a cell contains relatively few) and a ubiquitin–protein ligase (E3, of which there are possibly hundreds). Post-translational modifications of the protein substrate, such as phosphorylation or hydroxylation, are often required prior to its selection. In this way, the precise spatio-temporal targeting and degradation of a given substrate can be achieved. The E3s are a large, diverse group of proteins, characterized by one of several defining motifs. These include a HECT (homologous to E6-associated protein C-terminus), RING (really interesting new gene) or U-box (a modified RING motif without the full complement of Zn2+-binding ligands) domain. Whereas HECT E3s have a direct role in catalysis during ubiquitination, RING and U-box E3s facilitate protein ubiquitination. These latter two E3 types act as adaptor-like molecules. They bring an E2 and a substrate into sufficiently close proximity to promote the substrate's ubiquitination. Although many RING-type E3s, such as MDM2 (murine double minute clone 2 oncoprotein) and c-Cbl, can apparently act alone, others are found as components of much larger multi-protein complexes, such as the anaphase-promoting complex. Taken together, these multifaceted properties and interactions enable E3s to provide a powerful, and specific, mechanism for protein clearance within all cells of eukaryotic organisms. The importance of E3s is highlighted by the number of normal cellular processes they regulate, and the number of diseases associated with their loss of function or inappropriate targeting.


2014 ◽  
Vol 6 ◽  
pp. csb0001007 ◽  
Author(s):  
Michael J. Berridge
Keyword(s):  

Reproduction ◽  
2000 ◽  
pp. 221-228 ◽  
Author(s):  
HF Irving-Rodgers ◽  
RJ Rodgers

Different morphological phenotypes of follicular basal lamina and of membrana granulosa have been observed. Ten preantral follicles (< 0. 1 mm), and 17 healthy and six atretic antral follicles (0.5-12 mm in diameter) were processed for light and electron microscopy to investigate the relationship the between follicular basal lamina and membrana granulosa. Within each antral follicle, the shape of the basal cells of the membrana granulosa was uniform, and either rounded or columnar. There were equal proportions of follicles </= 4 mm in diameter with columnar basal cells and with rounded basal cells. Larger follicles had only rounded basal cells. Conventional basal laminae of a single layer adjacent to the basal granulosa cells were observed in healthy follicles at the preantral and antral stages. However, at the preantral stage, the conventional types of basal lamina were enlarged or even partially laminated. A second type of basal lamina, described as 'loopy', occurred in about half the preantral follicles and in half the antral follicles </= 4 mm diameter. 'Loopy' basal laminae were not observed in larger follicles. 'Loopy' basal laminae were composed of basal laminae aligning the basal surface of basal granulosa cells, but with additional layers or loops often branching from the innermost layer. Each loop was usually < 1 microm long and had vesicles (20-30 nm) attached to the inner aspect. Basal cellular processes were also common, and vesicles could be seen budding off from these processes. In antral follicles, conventional basal laminae occurred in follicles with rounded basal granulosa cells. Other follicles with columnar cells, and atretic follicles, had the 'loopy' basal lamina phenotype. Thus, follicles have different basal laminae that relate to the morphology of the membrana granulosa.


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