scholarly journals Computational analysis of GAL pathway pinpoints mechanisms underlying natural variation

2021 ◽  
Vol 17 (9) ◽  
pp. e1008691
Author(s):  
Jiayin Hong ◽  
Julius Palme ◽  
Bo Hua ◽  
Michael Springer
Keyword(s):  
In Silico ◽  
Quantitative Traits ◽  
Mechanistic Model ◽  
Behavioral Differences ◽  
Nutrient Metabolism ◽  
Tuning Parameters ◽  
Yeast Strains ◽  
Pathway Activation ◽  
Natural Variants ◽  
Different Strains

Quantitative traits are measurable phenotypes that show continuous variation over a wide phenotypic range. Enormous effort has recently been put into determining the genetic influences on a variety of quantitative traits with mixed success. We identified a quantitative trait in a tractable model system, the GAL pathway in yeast, which controls the uptake and metabolism of the sugar galactose. GAL pathway activation depends both on galactose concentration and on the concentrations of competing, preferred sugars such as glucose. Natural yeast isolates show substantial variation in the behavior of the pathway. All studied yeast strains exhibit bimodal responses relative to external galactose concentration, i.e. a set of galactose concentrations existed at which both GAL-induced and GAL-repressed subpopulations were observed. However, these concentrations differed in different strains. We built a mechanistic model of the GAL pathway and identified parameters that are plausible candidates for capturing the phenotypic features of a set of strains including standard lab strains, natural variants, and mutants. In silico perturbation of these parameters identified variation in the intracellular galactose sensor, Gal3p, the negative feedback node within the GAL regulatory network, Gal80p, and the hexose transporters, HXT, as the main sources of the bimodal range variation. We were able to switch the phenotype of individual yeast strains in silico by tuning parameters related to these three elements. Determining the basis for these behavioral differences may give insight into how the GAL pathway processes information, and into the evolution of nutrient metabolism preferences in different strains. More generally, our method of identifying the key parameters that explain phenotypic variation in this system should be generally applicable to other quantitative traits.

scholarly journals Computational analysis of GAL pathway pinpoints mechanisms underlying natural variation

2021 ◽  
Author(s):  
Jiayin Hong ◽  
Bo Hua ◽  
Michael Springer
Keyword(s):  
Negative Feedback ◽  
In Silico ◽  
Metabolic Regulation ◽  
Quantitative Traits ◽  
Natural Variation ◽  
Mechanistic Model ◽  
Ecological Niches ◽  
Yeast Strains ◽  
Hexose Transporters ◽  
Different Strains

AbstractQuantitative traits such as human height are measurable phenotypes that show continuous variation over a wide phenotypic range. Enormous effort has recently been put into determining the genetic influences on a variety of quantitative traits, including human genetic diseases, with mixed success. We identified a quantitative trait in a tractable model system, the GAL pathway in yeast, which controls the uptake and metabolism of the sugar galactose. GAL pathway activation depends both on galactose concentration and on the concentrations of competing, preferred sugars such as glucose. Natural yeast isolates show substantial variation in the behavior of the pathway. All studied yeast strains exhibit bimodal responses relative to external galactose concentration, i.e. a set of galactose concentrations existed at which both GAL-induced and GAL-repressed subpopulations were observed. However, these concentrations differed in different strains. We built a mechanistic model of the GAL pathway and identified parameters that are plausible candidates for capturing the phenotypic features of a set of strains including standard lab strains, natural variants, and mutants. In silico perturbation of these parameters identified variation in the intracellular galactose sensor, Gal3p, the negative feedback node within the GAL regulatory network, Gal80p, and the hexose transporters, HXT, as the main sources of the bimodal range variation. We were able to switch the phenotype of individual yeast strains in silico by tuning parameters related to these three elements. Determining the basis for these behavioral differences may give insight into how the GAL pathway processes information, and into the evolution of nutrient metabolism preferences in different strains. More generally, our method of identifying the key parameters that explain phenotypic variation in this system should be generally applicable to other quantitative traits.Author summaryMicrobes adopt elaborate strategies for the preferred uptake and use of nutrients to cope with complex and fluctuating environments. As a result, yeast strains originating from different ecological niches show significant variation in the way they induce genes in the galactose metabolism (GAL) pathway in response to nutrient signals. To identify the mechanistic sources of this variation, we built a mathematical model to simulate the dynamics of the galactose metabolic regulation network, and studied how parameters with different biological implications contributed to the natural variation. We found that variations in the behavior of the galactose sensor Gal3p, the negative feedback node Gal80p, and the hexose transporters HXT were critical elements in the GAL pathway response. Tuning single parameters in silico was sufficient to achieve phenotype switching between different yeast strains. Our computational approach should be generally useful to help pinpoint the genetic and molecular bases of natural variation in other systems.

Thermoresistance in black yeasts is associated with halosensitivity and HPP tolerance, but not with UV tolerance or sanitizer tolerance

2021 ◽  
Author(s):  
Shiyu Cai ◽  
Abigail Snyder
Keyword(s):  
Food Production ◽  
Uv Light ◽  
High Pressure Processing ◽  
Black Yeast ◽  
Black Yeasts ◽  
Strain Variation ◽  
Yeast Strains ◽  
Uv Tolerance ◽  
Relative Stress ◽  
Different Strains

Black yeasts can survive extreme conditions in food production owing to their polyextremotolerant character. However, significant strain-to-strain variation in black yeast thermoresistance has been observed. In this study, we assessed the variability in tolerance to nonthermal interventions among a collection of food-related black yeast strains. Variation in tolerance to UV light treatment, high pressure processing, sanitizers, and osmotic pressure was observed within each species. The two strains previously shown to possess high thermotolerance, Exophiala phaeomuriformis FSL-E2-0572 and Exophiala dermatitidis YB-734, were also the most HPP tolerant, but were the least halotolerant. Meanwhile, Aureobasidium pullulans FSL-E2-0290 was the most UV and sanitizer tolerant, but had been shown to have relatively low thermoresistance. Fisher’s exact tests showed that thermoresistance in black yeasts was associated with HPP tolerance and inversely with halotolerance, but no association was found with UV tolerance or sanitizer tolerance. Collectively, the relative stress tolerance among strains varied across interventions. Given this variation, a broad range of different food products are susceptible to black yeast spoilage. Additionally, different strains should be selected in challenge studies specific to the intervention. (1312/2000 characters)

Differentiation of Yeast Cultures in Ruminant Feedingstuffs Using a Rapid DNA Fingerprinting Technique

1994 ◽  
Vol 1994 ◽  
pp. 101-101
Author(s):  
Elizabeth Moore ◽  
Denis R. Headon
Keyword(s):  
Sodium Dodecyl ◽  
Yeast Cells ◽  
Microbial Populations ◽  
Yeast Culture ◽  
Yeast Cultures ◽  
Yeast Strains ◽  
Genetic Sequences ◽  
Polymerase Chain ◽  
Different Strains ◽  
Triton X

Research indicates that certain yeast strains are beneficial in their capacity to stimulate key microbial populations. This stimulation is strain specific with similar yeast strains exerting their effect on totally different microbial populations. Future yeast culture supplements may contain mixtures of different strains designed to suit specific diets. This, therefore, requires the development of a rapid sensitive technique to differentiate among taxonomically similar yeast strains in animal diets. This technique, termed the Randomly Amplified Polymorphic DNA (RAPD) assay, is based upon the use of randomly designed short polynucleotide primers to amplify genetic sequences from the DNA of the desired yeast strain. Our objective involves the development of this technique to distinguish between closely related yeast strains present in feed. The feed sample investigated was a standard cattle ration containing three strains of Saccharomyces cerevisiae (1026, 2045 and 2020) and Candida utilis 3001 at a concentration of 106 CFU/g respectively. Isolation of single colonies of yeast strains present was achieved by feed extraction in dilution buffer followed by plating a series of dilutions on rose-bengal agar. Thirty randomly selected colonies were cultured in YPD (1% yeast extract, 2% peptone, 2% glucose) broth for 24 - 30 hours at 30°C. Genomic DNA was isolated from yeast cells by standard methods based on subjection of the cells to vortex mixing in the presence of glass beads, triton X-100, sodium dodecyl sulphate, phenol and chloroform. Isolated DNA from randomly selected colonies was amplified by Polymerase Chain Reaction (PCR) for 45 cycles of 1 min at 94°C, 1 min at 36°C and 1 min at 72°C using randomly designed 10 bp primers.

scholarly journals Enhancing network activation in natural killer cells: predictions from in silico modeling

2020 ◽  
Vol 12 (5) ◽  
pp. 109-121
Author(s):  
Sahak Z Makaryan ◽  
Stacey D Finley
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
In Silico ◽  
Intracellular Signaling ◽  
Cell Activation ◽  
Nk Cell ◽  
Mechanistic Model ◽  
Cell Killing ◽  
Published Data ◽  
Network Activation

Abstract Natural killer (NK) cells are part of the innate immune system and are capable of killing diseased cells. As a result, NK cells are being used for adoptive cell therapies for cancer patients. The activation of NK cell stimulatory receptors leads to a cascade of intracellular phosphorylation reactions, which activates key signaling species that facilitate the secretion of cytolytic molecules required for cell killing. Strategies that maximize the activation of such intracellular species can increase the likelihood of NK cell killing upon contact with a cancer cell and thereby improve efficacy of NK cell-based therapies. However, due to the complexity of intracellular signaling, it is difficult to deduce a priori which strategies can enhance species activation. Therefore, we constructed a mechanistic model of the CD16, 2B4 and NKG2D signaling pathways in NK cells to simulate strategies that enhance signaling. The model predictions were fit to published data and validated with a separate dataset. Model simulations demonstrate strong network activation when the CD16 pathway is stimulated. The magnitude of species activation is most sensitive to the receptor’s initial concentration and the rate at which the receptor is activated. Co-stimulation of CD16 and NKG2D in silico required fewer ligands to achieve half-maximal activation than other combinations, suggesting co-stimulating these pathways is most effective in activating the species. We applied the model to predict the effects of perturbing the signaling network and found two strategies that can potently enhance network activation. When the availability of ligands is low, it is more influential to engineer NK cell receptors that are resistant to proteolytic cleavage. In contrast, for high ligand concentrations, inhibiting phosphatase activity leads to sustained species activation. The work presented here establishes a framework for understanding the complex, nonlinear aspects of NK cell signaling and provides detailed strategies for enhancing NK cell activation.

scholarly journals The Neuroproteomic Basis of Enhanced Perception and Processing of Brood Signals That Trigger Increased Reproductive Investment in Honeybee (Apis mellifera) Workers

2020 ◽  
Vol 19 (10) ◽  
pp. 1632-1648
Author(s):  
Xufeng Zhang ◽  
Han Hu ◽  
Bin Han ◽  
Qiaohong Wei ◽  
Lifeng Meng ◽  
...  
Keyword(s):  
Cognitive Processing ◽  
Royal Jelly ◽  
Reproductive Investment ◽  
Alloparental Care ◽  
Behavioral Differences ◽  
Nutrient Metabolism ◽  
Olfactory Conditioning ◽  
Proboscis Extension ◽  
Complex Social Behavior ◽  
Care Behavior

The neuronal basis of complex social behavior is still poorly understood. In honeybees, reproductive investment decisions are made at the colony-level. Queens develop from female-destined larvae that receive alloparental care from nurse bees in the form of ad-libitum royal jelly (RJ) secretions. Typically, the number of raised new queens is limited but genetic breeding of “royal jelly bees” (RJBs) for enhanced RJ production over decades has led to a dramatic increase of reproductive investment in queens. Here, we compare RJBs to unselected Italian bees (ITBs) to investigate how their cognitive processing of larval signals in the mushroom bodies (MBs) and antennal lobes (ALs) may contribute to their behavioral differences. A cross-fostering experiment confirms that the RJB syndrome is mainly due to a shift in nurse bee alloparental care behavior. Using olfactory conditioning of the proboscis extension reflex, we show that the RJB nurses spontaneously respond more often to larval odors compared with ITB nurses but their subsequent learning occurs at similar rates. These phenotypic findings are corroborated by our demonstration that the proteome of the brain, particularly of the ALs differs between RJBs and ITBs. Notably, in the ALs of RJB newly emerged bees and nurses compared with ITBs, processes of energy and nutrient metabolism, signal transduction are up-regulated, priming the ALs for receiving and processing the brood signals from the antennae. Moreover, highly abundant major royal jelly proteins and hexamerins in RJBs compared with ITBs during early life when the nervous system still develops suggest crucial new neurobiological roles for these well-characterized proteins. Altogether, our findings reveal that RJBs have evolved a strong olfactory response to larvae, enabled by numerous neurophysiological adaptations that increase the nurse bees' alloparental care behavior.

scholarly journals Comparative Transcriptomic Approach To Investigate Differences in Wine Yeast Physiology and Metabolism during Fermentation

2009 ◽  
Vol 75 (20) ◽  
pp. 6600-6612 ◽  
Author(s):  
Debra Rossouw ◽  
Roberto Olivares-Hernandes ◽  
Jens Nielsen ◽  
Florian F. Bauer
Keyword(s):  
Stress Responses ◽  
Metabolic Regulation ◽  
Wine Yeast ◽  
Molecular Networks ◽  
Comparative Approach ◽  
Phenotypic Traits ◽  
Phenotypic Differences ◽  
Yeast Strains ◽  
Industrial Strains ◽  
Different Strains

ABSTRACT Commercial wine yeast strains of the species Saccharomyces cerevisiae have been selected to satisfy many different, and sometimes highly specific, oenological requirements. As a consequence, more than 200 different strains with significantly diverging phenotypic traits are produced globally. This genetic resource has been rather neglected by the scientific community because industrial strains are less easily manipulated than the limited number of laboratory strains that have been successfully employed to investigate fundamental aspects of cellular biology. However, laboratory strains are unsuitable for the study of many phenotypes that are of significant scientific and industrial interest. Here, we investigate whether a comparative transcriptomics and phenomics approach, based on the analysis of five phenotypically diverging industrial wine yeast strains, can provide insights into the molecular networks that are responsible for the expression of such phenotypes. For this purpose, some oenologically relevant phenotypes, including resistance to various stresses, cell wall properties, and metabolite production of these strains were evaluated and aligned with transcriptomic data collected during alcoholic fermentation. The data reveal significant differences in gene regulation between the five strains. While the genetic complexity underlying the various successive stress responses in a dynamic system such as wine fermentation reveals the limits of the approach, many of the relevant differences in gene expression can be linked to specific phenotypic differences between the strains. This is, in particular, the case for many aspects of metabolic regulation. The comparative approach therefore opens new possibilities to investigate complex phenotypic traits on a molecular level.

scholarly journals Redox Interactions between Saccharomyces cerevisiae and Saccharomyces uvarum in Mixed Culture under Enological Conditions

2005 ◽  
Vol 71 (1) ◽  
pp. 255-260 ◽  
Author(s):  
Naoufel Cheraiti ◽  
St�phane Guezenec ◽  
Jean-Michel Salmon
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Mixed Culture ◽  
Wine Yeast ◽  
Redox Status ◽  
Product Formation ◽  
Hybrid Strain ◽  
Saccharomyces Uvarum ◽  
Yeast Strains ◽  
Different Strains ◽  
Different Cultures

ABSTRACT Wine yeast starters that contain a mixture of different industrial yeasts with various properties may soon be introduced to the market. The mechanisms underlying the interactions between the different strains in the starter during alcoholic fermentation have never been investigated. We identified and investigated some of these interactions in a mixed culture containing two yeast strains grown under enological conditions. The inoculum contained the same amount (each) of a strain of Saccharomyces cerevisiae and a natural hybrid strain of S. cerevisiae and Saccharomyces uvarum. We identified interactions that affected biomass, by-product formation, and fermentation kinetics, and compared the redox ratios of monocultures of each strain with that of the mixed culture. The redox status of the mixed culture differed from that of the two monocultures, showing that the interactions between the yeast strains involved the diffusion of metabolite(s) within the mixed culture. Since acetaldehyde is a potential effector of fermentation, we investigated the kinetics of acetaldehyde production by the different cultures. The S. cerevisiae-S. uvarum hybrid strain produced large amounts of acetaldehyde for which the S. cerevisiae strain acted as a receiving strain in the mixed culture. Since yeast response to acetaldehyde involves the same mechanisms that participate in the response to other forms of stress, the acetaldehyde exchange between the two strains could play an important role in inhibiting some yeast strains and allowing the growth of others. Such interactions could be of particular importance in understanding the ecology of the colonization of complex fermentation media by S. cerevisiae.

scholarly journals MCF-7 Human Breast Adenocarcinoma Anticancer and Antimicrobial, in silico Docking and ADME Prediction Studies of Furan Moiety Containing Substituted 2-Aminopyrimidine Derivatives

2021 ◽  
Vol 33 (7) ◽  
pp. 1504-1512
Author(s):  
Manju Mathew ◽  
Muthuvel Ramanathan Ezhilarasi
Keyword(s):  
In Silico ◽  
Antimicrobial Activities ◽  
Docking Studies ◽  
Breast Adenocarcinoma ◽  
Bacterial Strains ◽  
In Silico Docking ◽  
In Silico Studies ◽  
Furan Moiety ◽  
Different Strains

A series of 4(5-(4-chlorophenyl)furan-2-yl)-6-phenylpyrimidin-2-amine derivatives (5a-h) were synthesized from 2-(4-chlorophenyl)-5-styrylfuran (3a-h) with guanidine nitrate in absolute ethanol under conventional method and evaluated for their in vitro anticancer, antimicrobial activities and in silico studies. The chemical structure of the furan moiety containing substituted amino pyrimidine derivatives (5a-h) were elucidated from spectroscopic analysis like infrared, 1H & 13C NMR spectral data and CHN analysis. in silico docking studies were predicted for the synthesized compounds (5a-h) using bacterial protein 1UAG and in silico ADME predictions were also carried for the synthesized compounds (5a-h). The in vitro anticancer study was carried the compound 5b by MMT assay. Compound 5b shows the LC50 value of 120.15 ± 0.003 μg/mL. in vitro Antimicrobial activities were screened for the compounds (5a-h) using different strains. Compound 5h has electron withdrawing group in benzene ring substituted in the para position showed good antimicrobial activity against all the bacterial strains and fungal strains. in silico studies, compound 5h shows excellent docking score (-9.7 kcal/mol) compared with ciprofloxacin (-7.8 kcal/mol).

scholarly journals Evaluation of Saccharomyces pastorianus impact to Sauvignon blanc chemical & sensory profile compared to different strains of S. cerevisiae/bayanus

2019 ◽  
Vol 12 ◽  
pp. 02025
Author(s):  
V. Troianou ◽  
C. Toumpeki ◽  
E. Dorignac ◽  
C. Kogkou ◽  
S. Kallithraka ◽  
...  
Keyword(s):  
Sensory Profile ◽  
Higher Alcohols ◽  
Sauvignon Blanc ◽  
Wine Analysis ◽  
Yeast Strains ◽  
Saccharomyces Pastorianus ◽  
Cold Condition ◽  
Fermentation Parameters ◽  
Different Strains ◽  
The Impact

Enhancing flavors and/or improving fermentation parameters through the use of different species of yeast strains is nowadays a frequent challenge in winemaking research, especially for aromatic varieties such as Sauvignon Blanc. In this work, the aim was to focus on the impact of a species not already studied in wine: Saccharomyces pastorianus. Twenty-two fermentations were conducted on a Sauvignon Blanc must by addition of different strains and mixtures of them by using two different inoculation temperatures. The must was inoculated in cold condition with two similar mixtures of S. pastorianus 1 or 2 (70%) and S. bayanus(30%), with S. pastorianus 1 or 2 alone, with the correspondent S. bayanusalone and with two other S. cerevisiae1 and 2 alone as well. For classic condition, the must was inoculated with only one mixture S. pastorianus1 (70%) / S. bayanus(30%), and respectively with S. pastorianus1, S. bayanus and S. cerevisiae 2 alone. Samples were taken all along the fermentations for both conditions in order to check chemical and microbial analyses as well as yeast implantations. The final wines were analysed for alcohol, glucose, fructose, all other classical wine analysis as well as for acetate esters, and higher alcohols. The results underlined that for both S. pastorianus 1 and S. pastorianus 2 strains, the production of acetic acid was zero in cold condition and really low (0.09 g/l) for classic condition regarding S. pastorianus 1. As a consequence, Saccharomyces pastorianus seems to be highly interesting for winemaking, alone or in co-inoculation with S. bayanus.

scholarly journals Which Zebrafish Strains Are More Suitable to Perform Behavioral Studies? A Comprehensive Comparison by Phenomic Approach

Biology ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 200 ◽  
Author(s):  
Gilbert Audira ◽  
Petrus Siregar ◽  
Stefan-Adrian Strungaru ◽  
Jong-Chin Huang ◽  
Chung-Der Hsiao
Keyword(s):  
Coefficient Of Variation ◽  
Predator Avoidance ◽  
Principal Component ◽  
Behavioral Tests ◽  
Wild Type ◽  
Behavioral Differences ◽  
Behavioral Test ◽  
Behavioral Studies ◽  
Comprehensive Comparison ◽  
Different Strains

Wild-type (WT) zebrafish are commonly used in behavioral tests, however, the term WT corresponds to many different strains, such as AB, Tübingen long fin (TL), and Wild Indian Karyotype (WIK). Since these strains are widely used, there has to be at least one study to demonstrate the behavioral differences between them. In our study, six zebrafish strains were used, which are AB, absolute, TL, golden, pet store-purchased (PET), and WIK zebrafishes. The behavior of these fishes was tested in a set of behavioral tests, including novel tank, mirror-biting, predator avoidance, social interaction, and shoaling tests. From the results, the differences were observed for all behavioral tests, and each strain displayed particular behavior depending on the tests. In addition, from the heatmap and PCA (principal component analysis) results, two major clusters were displayed, separating the AB and TL zebrafishes with other strains in another cluster. Furthermore, after the coefficient of variation of each strain in every behavioral test was calculated, the AB and TL zebrafishes were found to possess a low percentage of the coefficient of variation, highlighting the strong reproducibility and the robustness of the behaviors tested in both fishes. Each zebrafish strain tested in this experiment showed specifically different behaviors from each other, thus, strain-specific zebrafish behavior should be considered when designing experiments using zebrafish behavior.

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