stochastic events
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2021 ◽  
Vol 8 ◽  
Author(s):  
Shelly Mahlab-Aviv ◽  
Nathan Linial ◽  
Michal Linial

A hallmark of cancer evolution is that the tumor may change its cell identity and improve its survival and fitness. Drastic change in microRNA (miRNA) composition and quantities accompany such dynamic processes. Cancer samples are composed of cells’ mixtures of varying stages of cancerous progress. Therefore, cell-specific molecular profiling represents cellular averaging. In this study, we consider the degree to which altering miRNAs composition shifts cell behavior. We used COMICS, an iterative framework that simulates the stochastic events of miRNA-mRNA pairing, using a probabilistic approach. COMICS simulates the likelihood that cells change their transcriptome following many iterations (100 k). Results of COMICS from the human cell line (HeLa) confirmed that most genes are resistant to miRNA regulation. However, COMICS results suggest that the composition of the abundant miRNAs dictates the nature of the cells (across three cell lines) regardless of its actual mRNA steady-state. In silico perturbations of cell lines (i.e., by overexpressing miRNAs) allowed to classify genes according to their sensitivity and resilience to any combination of miRNA perturbations. Our results expose an overlooked quantitative dimension for a set of genes and miRNA regulation in living cells. The immediate implication is that even relatively modest overexpression of specific miRNAs may shift cell identity and impact cancer evolution.


PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0260567
Author(s):  
Sarah Shandera ◽  
Jes L. Matsick ◽  
David R. Hunter ◽  
Louis Leblond

We propose a framework of Resources, Achievement, Status, and Events (RASE) that allows the many disparate but well-documented phenomena affecting underrepresented groups in STEM to be assembled into a story of career trajectories, illuminating the possible cumulative impact of many small inequities. Our framework contains a three-component deterministic cycle of (1) production of Achievements from Resources, (2) updated community Status due to Achievements, and (3) accrual of additional Resources based on community Status. A fourth component, stochastic Events, can influence an individual’s level of Resources or Achievements at each time step of the cycle. We build a specific mathematical model within the RASE framework and use it to investigate the impact of accumulated disadvantages from multiple compounding variables. We demonstrate that the model can reproduce data of observed disparities in academia. Finally, we use a publicly available visualization and networking tool to provide a sandbox for exploring career outcomes within the model. The modeling exercise, results, and visualization tool may be useful in the context of training STEM faculty to recognize and reduce effects of bias.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ulrich K. Steiner ◽  
Shripad Tuljapurkar ◽  
Deborah A. Roach

AbstractSimple demographic events, the survival and reproduction of individuals, drive population dynamics. These demographic events are influenced by genetic and environmental parameters, and are the focus of many evolutionary and ecological investigations that aim to predict and understand population change. However, such a focus often neglects the stochastic events that individuals experience throughout their lives. These stochastic events also influence survival and reproduction and thereby evolutionary and ecological dynamics. Here, we illustrate the influence of such non-selective demographic variability on population dynamics using population projection models of an experimental population of Plantago lanceolata. Our analysis shows that the variability in survival and reproduction among individuals is largely due to demographic stochastic variation with only modest effects of differences in environment, genes, and their interaction. Common expectations of population growth, based on expected lifetime reproduction and generation time, can be misleading when demographic stochastic variation is large. Large demographic stochastic variation exhibited within genotypes can lower population growth and slow evolutionary adaptive dynamics. Our results accompany recent investigations that call for more focus on stochastic variation in fitness components, such as survival, reproduction, and functional traits, rather than dismissal of this variation as uninformative noise.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Shidong Song ◽  
Alexander F. Mason ◽  
Richard A. J. Post ◽  
Marco De Corato ◽  
Rafael Mestre ◽  
...  

AbstractRandom fluctuations are inherent to all complex molecular systems. Although nature has evolved mechanisms to control stochastic events to achieve the desired biological output, reproducing this in synthetic systems represents a significant challenge. Here we present an artificial platform that enables us to exploit stochasticity to direct motile behavior. We found that enzymes, when confined to the fluidic polymer membrane of a core-shell coacervate, were distributed stochastically in time and space. This resulted in a transient, asymmetric configuration of propulsive units, which imparted motility to such coacervates in presence of substrate. This mechanism was confirmed by stochastic modelling and simulations in silico. Furthermore, we showed that a deeper understanding of the mechanism of stochasticity could be utilized to modulate the motion output. Conceptually, this work represents a leap in design philosophy in the construction of synthetic systems with life-like behaviors.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Debra Van Egeren ◽  
Alexander Novokhodko ◽  
Madison Stoddard ◽  
Uyen Tran ◽  
Bruce Zetter ◽  
...  

AbstractThe rapid emergence and expansion of novel SARS-CoV-2 variants threatens our ability to achieve herd immunity for COVID-19. These novel SARS-CoV-2 variants often harbor multiple point mutations, conferring one or more evolutionarily advantageous traits, such as increased transmissibility, immune evasion and longer infection duration. In a number of cases, variant emergence has been linked to long-term infections in individuals who were either immunocompromised or treated with convalescent plasma. In this paper, we used a stochastic evolutionary modeling framework to explore the emergence of fitter variants of SARS-CoV-2 during long-term infections. We found that increased viral load and infection duration favor emergence of such variants. While the overall probability of emergence and subsequent transmission from any given infection is low, on a population level these events occur fairly frequently. Targeting these low-probability stochastic events that lead to the establishment of novel advantageous viral variants might allow us to slow the rate at which they emerge in the patient population, and prevent them from spreading deterministically due to natural selection. Our work thus suggests practical ways to achieve control of long-term SARS-CoV-2 infections, which will be critical for slowing the rate of viral evolution.


2021 ◽  
Author(s):  
Thorsten Buch ◽  
Vladislava Milchevskaya ◽  
Philippe Bugnon ◽  
Emiel ten Buren ◽  
Frank Brand ◽  
...  

Abstract Animal breeding is time-consuming, costly, and affected by stochastic events related to Mendelian genetics, fertility, and litter size. Careful planning is mandatory to ensure a successful outcome using the least number of animals, hence adhering to the 3Rs of animal welfare. We have developed an R package, accessible also through an interactive website, that optimizes breeding design and provides a comprehensive report suitable for any breeder of genetically defined traits.


2021 ◽  
Vol 8 ◽  
Author(s):  
Edward J. Phlips ◽  
Susan Badylak ◽  
Natalie G. Nelson ◽  
Lauren M. Hall ◽  
Charles A. Jacoby ◽  
...  

This paper examines the character of phytoplankton blooms in a restricted sub-tropical lagoon along the Atlantic coast of central Florida. The results of the 23-year study (1997–2020) provide evidence for multiple types of variability in bloom activity, including cyclical patterns, stochastic events, and most prominently a regime shift in composition and intensity. Cyclical patterns (e.g., El Niño/La Niña periods) and stochastic events (e.g., tropical storms) influenced rainfall levels, which in turn impacted nutrient concentrations in the water column and the timing and intensity of blooms. In 2011, a major change occurred in the character of blooms, with a dramatic increase in peak biomass levels of blooms and the appearance of new dominant taxa, including the brown tide species Aureoumbra lagunensis and other nanoplanktonic species. Results of quantitative analyses reveal system behavior indicative of a regime shift. The shift coincided with widespread losses of seagrass community and reduced drift algae biomass. A combination of exceptionally low water temperatures in the winters of 2009/2010 and 2010/2011, hypersaline conditions associated with drought conditions, and high light attenuation caused by blooms appear to have contributed to the widespread and protracted decline in seagrass and drift macroalgal communities in the lagoon, leading to shifts in distribution of internal and external nutrient sources toward phytoplankton.


2021 ◽  
Author(s):  
Mikhail Pavlenok ◽  
Luning Yu ◽  
Dominik Herrmann ◽  
Meni Wanunu ◽  
Michael Niederweis

Transmembrane protein channels enable fast and highly sensitive electrical detection of single molecules. Nanopore sequencing of DNA was achieved using an engineered Mycobacterium smegmatis porin A (MspA) in combination with a motor enzyme. Due to its favorable channel geometry, the octameric MspA pore exhibits the highest current level as compared to other pore proteins. To date, MspA is the only protein nanopore with a published record of DNA sequencing. While widely used in commercial devices, nanopore sequencing of DNA suffers from significant base-calling errors due to stochastic events of the complex DNA-motor-pore combination and the contribution of up to five nucleotides to the signal at each position. Asymmetric mutations within subunits of the channel protein offer an enormous potential to improve nucleotide resolution and sequencing accuracy. However, random subunit assembly does not allow control of the channel composition of MspA and other oligomeric protein pores. In this study, we showed that it is feasible to convert octameric MspA into a single-chain pore by connecting eight subunits using peptide linkers. We constructed single-chain MspA trimers, pentamers, hexamers and heptamers to demonstrate that it is feasible to alter the subunit stoichiometry and the MspA pore diameter. All single-chain MspA proteins formed functional channels in lipid bilayer experiments. Importantly, we demonstrated that single-chain MspA discriminated all four nucleotides identical to MspA produced from monomers. Thus, single-chain MspA constitutes a new milestone in its development and adaptation as a biosensor for DNA sequencing and many other applications.


2021 ◽  
Vol 55 (1) ◽  
Author(s):  
Leor Eshed Williams

Plants exhibit remarkable lineage plasticity, allowing them to regenerate organs that differ from their respective origins. Such developmental plasticity is dependent on the activity of pluripotent founder cells or stem cells residing in meristems. At the shoot apical meristem (SAM), the constant flow of cells requires continuing cell specification governed by a complex genetic network, with the WUSCHEL transcription factor and phytohormone cytokinin at its core. In this review, I discuss some intriguing recent discoveries that expose new principles and mechanisms of patterning and cell specification acting both at the SAM and, prior to meristem organogenesis during shoot regeneration. I also highlight unanswered questions and future challenges in the study of SAM and meristem regeneration. Finally, I put forward a model describing stochastic events mediated by epigenetic factors to explain how the gene regulatory network might be initiated at the onset of shoot regeneration. Expected final online publication date for the Annual Review of Genetics, Volume 55 is November 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.


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