Correct decision making is fundamental for all living organisms to thrive under environmental changes. The patterns of environmental variation and the quality of available information define the most ...favourable strategy among multiple options, from randomly adopting a phenotypic state to sensing and reacting to environmental cues. Cellular memory-the ability to track and condition the time to switch to a different phenotypic state-can help withstand environmental fluctuations. How does memory manifest itself in unicellular organisms? We describe the population-wide consequences of phenotypic memory in microbes through a combination of deterministic modelling and stochastic simulations. Moving beyond binary switching models, our work highlights the need to consider a broader range of switching behaviours when describing microbial adaptive strategies. We show that memory in individual cells generates patterns at the population level coherent with overshoots and non-exponential lag times distributions experimentally observed in phenotypically heterogeneous populations. We emphasise the implications of our work in understanding antibiotic tolerance and, in general, bacterial survival under fluctuating environments.
Evolutionary games in the multiverse Gokhale, Chaitanya S; Traulsen, Arne
Proceedings of the National Academy of Sciences - PNAS,
03/2010, Volume:
107, Issue:
12
Journal Article
Peer reviewed
Open access
Evolutionary game dynamics of two players with two strategies has been studied in great detail. These games have been used to model many biologically relevant scenarios, ranging from social dilemmas ...in mammals to microbial diversity. Some of these games may, in fact, take place between a number of individuals and not just between two. Here we address one-shot games with multiple players. As long as we have only two strategies, many results from two-player games can be generalized to multiple players. For games with multiple players and more than two strategies, we show that statements derived for pairwise interactions no longer hold. For two-player games with any number of strategies there can be at most one isolated internal equilibrium. For any number of players Formula with any number of strategies Formula , there can be at most Formula isolated internal equilibria. Multiplayer games show a great dynamical complexity that cannot be captured based on pairwise interactions. Our results hold for any game and can easily be applied to specific cases, such as public goods games or multiplayer stag hunts.
•Firefly algorithm is efficient to coordinate over current relays.•Chaotic Firefly algorithm using tent maps is superior to the Firefly algorithm.•Initialization of random factor alpha near unity ...gives the best results.•Chaotic number generation is better than randomly generated numbers for relay coordination.
Over-current relays provide primary as well as backup protection to electrical distribution systems. These relays should be coordinated and set at the optimum values, to minimize the total operating time and hence ensure that least damage is caused when a fault occurs. While they provide backup protection, it is also imperative to ensure that their settings should not cause their inadvertent operation and subsequent sympathy trips.
This paper describes a Chaotic Firefly algorithm (CFA) for optimal time coordination of these relays. The algorithm has been implemented in MATLAB and tested on several systems, out of which two have been illustrated in this paper. The results obtained by the Chaotic Firefly algorithm are compared with those obtained by the conventional Firefly algorithm (FA). The novel feature of this paper is the application of the Chaotic Firefly algorithm to the problem of over-current relay coordination.
Epidemiology of keratoconus Gokhale, Nikhil
Indian journal of ophthalmology,
08/2013, Volume:
61, Issue:
8
Journal Article
Peer reviewed
Open access
Prevalence of keratoconus is variable in different parts of the world. Environmental and ethnic factors and the cohort of patients selected for such studies may explain the wide variation in the ...reported rates. Family history, gender differences, asymmetry in the two eyes, association with ocular rubbing, and natural history of disease are discussed.
Since its origins, thousands of years ago, agriculture has been challenged by the presence of evolving plant pathogens. Temporal rotations of host and non-host crops have helped farmers to control ...epidemics among other utilities, but further efforts for strategy assessment are needed. Here, we present a methodology for developing crop rotation strategies optimal for control of pathogens informed by numerical simulations of eco-evolutionary dynamics in one field. This approach can integrate agronomic criteria used in crop rotations-soil quality and cash yield-and the analysis of pathogen evolution in systems where hosts are artificially selected. Our analysis shows which rotation patterns perform better in maximising crop yield when an unspecified infection occurs, with yield being dependent on both soil quality and the strength of the epidemic. Importantly, the use of non-host crops, which both improve soil quality and control the epidemic results in similar rational rotation strategies for diverse agronomic and infection conditions. We test the repeatability of the best rotation patterns over multiple decades, an essential end-user goal. Our results provide sustainable strategies for optimal resource investment for increased food production and lead to further insights into the minimisation of pesticide use in a society demanding ever more efficient agriculture.
N6-methyladenosine (m⁶A) RNA methylation is the most abundant epitranscriptomic modification of eukaryotic messenger RNAs (mRNAs). Previous reports have found m⁶A on both cellular and viral ...transcripts and defined its role in regulating numerous biological processes, including viral infection. Here, we show that m⁶A and its associated machinery regulate the life cycle of hepatitis B virus (HBV). HBV is a DNA virus that completes its life cycle via an RNA intermediate, termed pregenomic RNA (pgRNA). Silencing of enzymes that catalyze the addition of m⁶A to RNA resulted in increased HBV protein expression, but overall reduced reverse transcription of the pgRNA. We mapped the m⁶A site in the HBV RNA and found that a conserved m⁶A consensus motif situated within the epsilon stem loop structure, is the site for m⁶A modification. The epsilon stem loop is located in the 3′ terminus of all HBV mRNAs and at both the 5′ and 3′ termini of the pgRNA. Mutational analysis of the identified m⁶A site in the 5′ epsilon stem loop of pgRNA revealed that m⁶A at this site is required for efficient reverse transcription of pgRNA, while m⁶A methylation of the 3′ epsilon stem loop results in destabilization of all HBV transcripts, suggesting that m⁶A has dual regulatory function for HBV RNA. Overall, this study reveals molecular insights into how m⁶A regulates HBV gene expression and reverse transcription, leading to an increased level of understanding of the HBV life cycle.
RNA modifications go viral Gokhale, Nandan S; Horner, Stacy M
PLoS pathogens,
03/2017, Volume:
13, Issue:
3
Journal Article
Peer reviewed
Open access
About the Authors: Nandan S. Gokhale Affiliation: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, United States of America Stacy M. Horner * ...E-mail: stacy.horner@duke.edu Affiliations Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, United States of America, Department of Medicine, Duke University Medical Center, Durham, North Carolina, United States of America ORCID http://orcid.org/0000-0002-9351-7409Citation: Gokhale NS, Horner SM (2017) RNA modifications go viral. Funding: Research in the Horner Lab is supported by the National Institutes of Health (R01AI125416, R21NS100545, and R21AI124100), the Duke University Center for AIDS Research (P30AI064518), and a Duke School of Medicine Whitehead Scholarship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. ...the microRNA miR-122 interacts with the viral RNA genome of hepatitis C virus (HCV) and is required for HCV replication 1. The deposition of m6A at the consensus motif DRAmCH (where D = G/A/U, R = G > A, and H = U/C/A) is governed by a cellular methyltransferase complex composed of the “writers” METTL3 and METTL14, and other noncatalytic cofactors. m6A modification can be reversed by the “erasers” FTO and ALKBH5. *We note that FTO has recently been found to have greater specificity for the m6Am modifications present in mRNA cap structures than for m6A 34. The role of m6A and the m6A machinery in RNA function and biological processes is further reviewed in 2. https://doi.org/10.1371/journal.ppat.1006188.g001 A role for m6A in viral...
Eco-evolutionary dynamics of social dilemmas Gokhale, Chaitanya S.; Hauert, Christoph
Theoretical population biology,
October 2016, 2016-10-00, 20161001, Volume:
111
Journal Article
Peer reviewed
Open access
Social dilemmas are an integral part of social interactions. Cooperative actions, ranging from secreting extra-cellular products in microbial populations to donating blood in humans, are costly to ...the actor and hence create an incentive to shirk and avoid the costs. Nevertheless, cooperation is ubiquitous in nature. Both costs and benefits often depend non-linearly on the number and types of individuals involved—as captured by idioms such as ‘too many cooks spoil the broth’ where additional contributions are discounted, or ‘two heads are better than one’ where cooperators synergistically enhance the group benefit. Interaction group sizes may depend on the size of the population and hence on ecological processes. This results in feedback mechanisms between ecological and evolutionary processes, which jointly affect and determine the evolutionary trajectory. Only recently combined eco-evolutionary processes became experimentally tractable in microbial social dilemmas. Here we analyse the evolutionary dynamics of non-linear social dilemmas in settings where the population fluctuates in size and the environment changes over time. In particular, cooperation is often supported and maintained at high densities through ecological fluctuations. Moreover, we find that the combination of the two processes routinely reveals highly complex dynamics, which suggests common occurrence in nature.
The recurrent interaction of skin with sunlight is an intrinsic constituent of human life, and exhibits both beneficial and detrimental effects. The apparent robust architectural framework of skin ...conceals remarkable mechanisms that operate at the interface between the surface and environment. In this Review, we discuss three distinct protective mechanisms and response pathways that safeguard skin from deleterious effects of ultraviolet (UV) radiation. The unique stratified epithelial architecture of human skin along with the antioxidant-response pathways constitutes the important defense mechanisms against UV radiation. The intricate pigmentary system and its intersection with the immune-system cytokine axis delicately balance tissue homeostasis. We discuss the relationship among these networks in the context of an unusual depigmenting disorder, vitiligo. The elaborate tunable mechanisms, elegant multilayered architecture and evolutionary selection pressures involved in skin and sunlight interaction makes this a compelling model to understand biological complexity.
Therapeutic methods to modulate skin pigmentation has important implications for skin cancer prevention and for treating cutaneous hyperpigmentary conditions. Towards defining new potential targets, ...we followed temporal dynamics of melanogenesis using a cell-autonomous pigmentation model. Our study elucidates 3 dominant phases of synchronized metabolic and transcriptional reprogramming. The melanogenic trigger is associated with high MITF levels along with rapid uptake of glucose. The transition to pigmented state is accompanied by increased glucose channelisation to anabolic pathways that support melanosome biogenesis. SREBF1-mediated up-regulation of fatty acid synthesis results in a transient accumulation of lipid droplets and enhancement of fatty acids oxidation through mitochondrial respiration. While this heightened bioenergetic activity is important to sustain melanogenesis, it impairs mitochondria lately, shifting the metabolism towards glycolysis. This recovery phase is accompanied by activation of the NRF2 detoxication pathway. Finally, we show that inhibitors of lipid metabolism can resolve hyperpigmentary conditions in a guinea pig UV-tanning model. Our study reveals rewiring of the metabolic circuit during melanogenesis, and fatty acid metabolism as a potential therapeutic target in a variety of cutaneous diseases manifesting hyperpigmentary phenotype.
PDF
