scholarly journals Heterosis is a systemic property emerging from nonlinear genotype-phenotype relationships: evidence from in vitro genetics and computer simulations

2017 ◽  
Author(s):  
Julie B. Fiévet ◽  
Thibault Nidelet ◽  
Christine Dillmann ◽  
Dominique de Vienne
Keyword(s):  
Genetic Variability ◽  
Point Of View ◽  
Crucial Issue ◽  
Metabolic Fluxes ◽  
Input Flux ◽  
Metabolic Systems ◽  
Realistic Situation ◽  
Systemic Property ◽  
Positive Heterosis

AbstractHeterosis, the superiority of hybrids over their parents for quantitative traits, represents a crucial issue in plant and animal breeding. Heterosis has given rise to countless genetic, genomic and molecular studies, but has rarely been investigated from the point of view of systems biology. We hypothesized that heterosis is an emergent property of living systems resulting from frequent concave relationships between genotypic variables and phenotypes, or between different phenotypic levels. We chose the enzyme-flux relationship as a model of the concave genotype-phenotype (GP) relationship, and showed that heterosis can be easily created in the laboratory. First, we reconstituted in vitro the upper part of glycolysis. We simulated genetic variability of enzyme activity by varying enzyme concentrations in test tubes. Mixing the content of “parental” tubes resulted in “hybrids”, whose fluxes were compared to the parental fluxes. Frequent heterotic fluxes were observed, under conditions that were determined analytically and confirmed by computer simulation. Second, to test this model in a more realistic situation, we modeled the glycolysis/fermentation network in yeast by considering one input flux, glucose, and two output fluxes, glycerol and acetaldehyde. We simulated genetic variability by randomly drawing parental enzyme concentrations under various conditions, and computed the parental and hybrid fluxes using a system of differential equations. Again we found that a majority of hybrids exhibited positive heterosis for metabolic fluxes. Cases of negative heterosis were due to local convexity between certain enzyme concentrations and fluxes. In both approaches, heterosis was maximized when the parents were phenotypically close and when the distributions of parental enzyme concentrations were contrasted and constrained. These conclusions are not restricted to metabolic systems: they only depend on the concavity of the GP relationship, which is commonly observed at various levels of the phenotypic hierarchy, and could account for the pervasiveness of heterosis.

Enzyme Promiscuous Activity: How to Define it and its Evolutionary Aspects

2020 ◽  
Vol 27 (5) ◽  
pp. 400-410
Author(s):  
Valentina De Luca ◽  
Luigi Mandrich
Keyword(s):  
Gene Evolution ◽  
Sequence Divergence ◽  
High Specificity ◽  
Industrial Applications ◽  
Point Of View ◽  
Enzyme Promiscuity ◽  
Primary Activity ◽  
Starting Point ◽  
Main Activity

: Enzymes are among the most studied biological molecules because better understanding enzymes structure and activity will shed more light on their biological processes and regulation; from a biotechnological point of view there are many examples of enzymes used with the aim to obtain new products and/or to make industrial processes less invasive towards the environment. Enzymes are known for their high specificity in the recognition of a substrate but considering the particular features of an increasing number of enzymes this is not completely true, in fact, many enzymes are active on different substrates: this ability is called enzyme promiscuity. Usually, promiscuous activities have significantly lower kinetic parameters than to that of primary activity, but they have a crucial role in gene evolution. It is accepted that gene duplication followed by sequence divergence is considered a key evolutionary mechanism to generate new enzyme functions. In this way, promiscuous activities are the starting point to increase a secondary activity in the main activity and then get a new enzyme. The primary activity can be lost or reduced to a promiscuous activity. In this review we describe the differences between substrate and enzyme promiscuity, and its rule in gene evolution. From a practical point of view the knowledge of promiscuity can facilitate the in vitro progress of proteins engineering, both for biomedical and industrial applications. In particular, we report cases regarding esterases, phosphotriesterases and cytochrome P450.

Insecticidal Active Rotenoids from Plant Parts and Callus Culture of Medicago sativa L. from a Semiarid Region of India (Rajasthan)

2020 ◽  
Vol 16 (6) ◽  
pp. 937-941
Author(s):  
Sharad Vats ◽  
Preeti Mehra
Keyword(s):  
Medicago Sativa ◽  
Callus Culture ◽  
Point Of View ◽  
Semiarid Region ◽  
Disease Vectors ◽  
Vector Borne Diseases ◽  
Plant Parts ◽  
Resistant Varieties ◽  
Medicago Sativa L

Background: Vector-borne diseases are quite prevalent globally and are one of the major causes of deaths due to infectious diseases. There is an availability of synthetic insecticides, however, their excessive and indiscriminate use have resulted in the emergence of resistant varieties of insects. Thus, a search for novel biopesticide has become inevitable. Methods: Rotenoids were isolated and identified from different parts of Medicago sativa L. This group of metabolites was also identified in the callus culture, and the rotenoid content was monitored during subculturing for a period of 10 months. Enhancement of the rotenoid content was evaluated by feeding precursors in a tissue culture medium. Results: Four rotenoids (elliptone, deguelin, rotenone and Dehydrorotenone) were identified, which were confirmed using spectral and chromatographic techniques. The maximum rotenoid content was found in the seeds (0.33±0.01%), followed by roots (0.31±0.01%) and minimum in the aerial parts (0.20±0.05%). A gradual decrease in the rotenoid content was observed with the ageing of subcultured tissue maintained for 10 months. The production of rotenoids was enhanced up to 2 folds in the callus culture using amino acids, Phenylalanine and Methionine as precursors as compared to the control. The LC50 value of the rotenoids was found to be 91 ppm and 162 ppm against disease vectors of malaria and Dracunculiasis, respectively. Conclusion: The study projects M. sativa as a novel source of biopesticide against the disease vectors of malaria and Dracunculiasis. The use of precursors to enhance the rotenoid content in vitro can be an effective venture from a commercial point of view.

scholarly journals Analysis of the Genetic Variability of Virulence-Related Loci in Epidemic Clones of Methicillin-Resistant Staphylococcus aureus

2005 ◽  
Vol 49 (1) ◽  
pp. 366-379 ◽  
Author(s):  
A. R. Gomes ◽  
S. Vinga ◽  
M. Zavolan ◽  
H. de Lencastre
Keyword(s):  
Staphylococcus Aureus ◽  
Genetic Variability ◽  
Amino Acid Level ◽  
Point Of View ◽  
Sequence Motifs ◽  
Related Factors ◽  
Specific Sequence ◽  
Methicillin Resistant ◽  
Sequence Types ◽  
R Domain

ABSTRACT Methicillin-resistant Staphylococcus aureus (MRSA) isolates have previously been classified into major epidemic clonal types by pulsed-field gel electrophoresis in combination with multilocus sequence typing (MLST) and staphylococcal cassette chromosome mec typing. We aimed to investigate whether genetic variability in potentially polymorphic domains of virulence-related factors could provide another level of differentiation in a diverse collection of epidemic MRSA clones. The target regions of strains representative of epidemic clones and genetically related methicillin-susceptible S. aureus isolates from the 1960s that were sequenced included the R domains of clfA and clfB; the D, W, and M regions of fnbA and fnbB; and three regions in the agr operon. Sequence variation ranged from very conserved regions, such as those for RNAIII and the agr interpromoter region, to the highly polymorphic R regions of the clf genes. The sequences of the clf R domains could be grouped into six major sequence types on the basis of the sequences in their 3′ regions. Six sequence types were also observed for the fnb sequences at the amino acid level. From an evolutionary point of view, it was interesting that a small DNA stretch at the 3′ clf R-domain sequence and the fnb sequences agreed with the results of MLST for this set of strains. In particular, clfB R-domain sequences, which had a high discriminatory capacity and with which the types distinguished were congruent with those obtained by other molecular typing methods, have potential for use for the typing of S. aureus. Clone- and strain-specific sequence motifs in the clf and fnb genes may represent useful additions to a typing methodology with a DNA array.

scholarly journals Potential of Probiotic Frozen Blackcurrant Products: Consumer Preference, Physicochemical Characterization, and Cell Viability

Foods ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 792
Author(s):  
Kati Väkeväinen ◽  
Noora Rinkinen ◽  
Roosa-Maria Willman ◽  
Jenni Lappi ◽  
Kaisa Raninen ◽  
...  
Keyword(s):  
Storage Time ◽  
Physicochemical Characterization ◽  
Consumer Preference ◽  
Nutritional Composition ◽  
Point Of View ◽  
Raw Material ◽  
Frozen Food ◽  
High Viability ◽  
Food Applications

Blackcurrant is a healthy, affordable, and traditionally gardened berry that, thus far, has been underused in food applications. From the consumers’ point of view, the acidic taste of blackcurrants is a challenge; therefore, these berries have mainly been utilized for sugary juice production. This research study aimed to develop a frozen vegan blackcurrant product with pleasant sensory properties and potential probiotic function. A candidate probiotic, Lactoplantibacillus plantarum Q823, was used in the manufacturing process. The physicochemical properties, nutritional composition, and consumer preference for the developed product were assessed, as was the viability of L. plantarum Q823 during storage time and in an in vitro gastrointestinal model. Consumers (n = 71) perceived the developed product to be pleasant. L. plantarum Q823 had high viability counts (log colony forming units (cfu) g−1 7.0 ± 0.38) in the final product, although the viability of L. plantarum Q823 during storage time needs to be enhanced to obtain a probiotic product. Thus, within an optimized formulation, blackcurrant berries represent a potential raw material for functional frozen food products.

scholarly journals Insights into the Antioxidant Mechanism of Newly Synthesized Benzoxazinic Nitrones: In Vitro and In Silico Studies with DPPH Model Radical

Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1224
Author(s):  
Stefania Marano ◽  
Cristina Minnelli ◽  
Lorenzo Ripani ◽  
Massimo Marcaccio ◽  
Emiliano Laudadio ◽  
...  
Keyword(s):  
Antioxidant Activity ◽  
Epr Spectroscopy ◽  
Point Of View ◽  
Uv Spectrophotometry ◽  
Design And Synthesis ◽  
Antioxidant Mechanism ◽  
Primary Mechanism ◽  
In Silico Studies ◽  
Wide Range

Synthetic nitrone spin-traps are being explored as therapeutic agents for the treatment of a wide range of oxidative stress-related pathologies, including but not limited to stroke, cancer, cardiovascular, and neurodegenerative diseases. In this context, increasing efforts are currently being made to the design and synthesis of new nitrone-based compounds with enhanced efficacy. The most researched nitrones are surely the ones related to α-phenyl-tert-butylnitrone (PBN) and 5,5-dimethyl-1-pyrroline N-oxide (DMPO) derivatives, which have shown to possess potent biological activity in many experimental animal models. However, more recently, nitrones with a benzoxazinic structure (3-aryl-2H-benzo[1,4]oxazin-N-oxides) have been demonstrated to have superior antioxidant activity compared to PBN. In this study, two new benzoxazinic nitrones bearing an electron-withdrawing methoxycarbonyl group on the benzo moiety (in para and meta positions respect to the nitronyl function) were synthesized. Their in vitro antioxidant activity was evaluated by two cellular-based assays (inhibition of AAPH-induced human erythrocyte hemolysis and cell death in human retinal pigmented epithelium (ARPE-19) cells) and a chemical approach by means of the α,α-diphenyl-β-picrylhydrazyl (DPPH) scavenging assay, using both electron paramagnetic resonance (EPR) spectroscopy and UV spectrophotometry. A computational approach was also used to investigate their potential primary mechanism of antioxidant action, as well as to rationalize the effect of functionalization on the nitrones reactivity toward DPPH, chosen as model radical in this study. Further insights were also gathered by exploring the nitrone electrochemical properties via cyclic voltammetry and by studying their kinetic behavior by means of EPR spectroscopy. Results showed that the introduction of an electron-withdrawing group in the phenyl moiety in the para position significantly increased the antioxidant capacity of benzoxazinic nitrones both in cell and cell-free systems. From the mechanistic point of view, the calculated results closely matched the experimental findings, strongly suggesting that the H-atom transfer (HAT) is likely to be the primary mechanism in the DPPH quenching.

Biocatalytic synthesis of terpene esters and their biological activity in human glioma cells

2021 ◽  
Vol 22 ◽  
Author(s):  
Mateusz Kutyła ◽  
Aleksandra Maciejczyk ◽  
Mariusz Trytek ◽  
Joanna Jakubowicz-Gil
Keyword(s):  
Cell Death ◽  
Apoptotic Cell ◽  
Fold Increase ◽  
Point Of View ◽  
Terpene Alcohols ◽  
Human Glioblastoma Multiforme ◽  
Anti Cancer ◽  
Therapeutic Molecules ◽  
Resistance To Chemotherapy

Background: Gliomas are highly malignant brain tumors with high resistance to chemotherapy. Therefore, investigations of new therapeutic molecules with high anti-glioma activity are of great importance. Objective: In this work, biocatalytic esterification of terpene alcohols with proven anti-cancer activity was performed to enhance their potency to induce cell death in human glioblastoma multiforme T98G and anaplastic astrocytoma MOGGCCM cell lines in vitro. Method and Results: We used primary terpene alcohols and carboxylic acids with a length of two to nine carbon atoms. The structure of the drinks influenced the esterification efficiency, which decreased in the following order: monocyclic > linear > bicyclic. Terpene alcohols and their esters only induced apoptotic cell death, which is highly desirable from a therapeutic point of view but did not induce autophagy and necrosis. The esterification of perillyl alcohol with butyric acid caused a 4-fold increase in cell death induction in the T98G line. Citronellol valerate, caprylate, and pelargonate and myrtenol butyrate, caprylate, and pelargonate also showed higher activity than their alcohol precursors. Conclusion: We have herein shown that esterification of natural alcohols by biocatalysis can improve the activity for other compounds investigated for their anti-glioma activity.

scholarly journals Screening of mucoadhesive vaginal gel formulations

2014 ◽  
Vol 50 (4) ◽  
pp. 931-941 ◽  
Author(s):  
Ana Ochoa Andrade ◽  
María Emma Parente ◽  
Gastón Ares
Keyword(s):  
Xanthan Gum ◽  
Rational Design ◽  
Point Of View ◽  
Vaginal Fluid ◽  
Multiple Factor Analysis ◽  
Vaginal Drug Delivery ◽  
Rheological Measurements ◽  
Gel Formulations ◽  
Positive Results

Rational design of vaginal drug delivery formulations requires special attention to vehicle properties that optimize vaginal coating and retention. The aim of the present work was to perform a screening of mucoadhesive vaginal gels formulated with carbomer or carrageenan in binary combination with a second polymer (carbomer, guar or xanthan gum). The gels were characterised using in vitroadhesion, spreadability and leakage potential studies, as well as rheological measurements (stress and frequency sweep tests) and the effect of dilution with simulated vaginal fluid (SVF) on spreadability. Results were analysed using analysis of variance and multiple factor analysis. The combination of polymers enhanced adhesion of both primary gelling agents, carbomer and carrageenan. From the rheological point of view all formulations presented a similar behaviour, prevalently elastic and characterised by loss tangent values well below 1. No correlation between rheological and adhesion behaviour was found. Carbomer and carrageenan gels containing the highest percentage of xanthan gum displayed good in vitro mucoadhesion and spreadability, minimal leakage potential and high resistance to dilution. The positive results obtained with carrageenan-xanthan gum-based gels can encourage the use of natural biocompatible adjuvants in the composition of vaginal products, a formulation field that is currently under the synthetic domain.

scholarly journals In vitro Propagation and Assessment of Genetic Relationships of Citrus Rootstocks Using ISSR Molecular Markers

2017 ◽  
Vol 45 (2) ◽  
pp. 383-391 ◽  
Author(s):  
Constantinos SALIS ◽  
Ioannis E. PAPADAKIS ◽  
Spyridon KINTZIOS ◽  
Marianna HAGIDIMITRIOU
Keyword(s):  
Molecular Markers ◽  
Genetic Variability ◽  
Root Length ◽  
In Vitro Propagation ◽  
Genetic Relationships ◽  
Shoot Proliferation ◽  
Poncirus Trifoliata ◽  
Naphthaleneacetic Acid ◽  
Issr Molecular Markers

The behavior of six citrus rootstocks, Volkameriana, Citrumelo ‘Swingle’, Citrange ‘Carrizo’, Poncirus trifoliata ‘Serra’, Poncirus trifoliata ‘Rubidoux’ and Poncirus trifoliata ‘Flying Dragon’, in in vitro propagation was studied and compared for shoot proliferation and rooting. In addition, the genetic relationships among the rootstocks studied and other Citrus species, using the Inter-Simple Sequence Repeats (ISSR) molecular markers, were investigated. Nodal explants of three months old shoots were used in Murashige and Skoog medium supplemented with N6-benzyladenine (BA) for shoot proliferation and with naphthaleneacetic acid (NAA) for rooting. The rootstock Volkameriana showed a statistically significant higher number of shoots (1.81), shoot length (15.14 mm) and number of leaves per explant (5.81), while all three Poncirus trifoliata rootstocks showed the lowest numbers. The number of roots and root length per explant were evaluated at the end of the rooting phase. The rootstock ‘Swingle’ showed a higher number of roots per explant (4.2) followed by ‘Flying Dragon’ (3.93) and ‘Carrizo’ (3.23) rootstocks. The rootstocks ‘Swingle’ (140.8 mm), Volkameriana (148 mm) and ‘Flying Dragon’ (131.12 mm) had significantly higher root length per explant compared to ‘Carrizo’ (31 mm) and ‘Rubidoux’ (34.5 mm). The ISSR molecular marker technique used in the present study grouped successfully the different species, varieties and rootstocks studied, revealing their genetic variability. The genetic variability observed among the rootstocks ranged between 0.29 (Poncirus trifoliata ‘Serra’ and Citrumelo ‘Swingle’) and 0.60 (Volkameriana and Citrumelo ‘Swingle’). The response of the rootstocks studied in in vitro propagation however is not related to their genetic affinity.

scholarly journals “Shepherd’s crook” neurons drive and synchronize the enhancing and suppressive mechanisms of the midbrain stimulus selection network

2018 ◽  
Vol 115 (32) ◽  
pp. E7615-E7623 ◽  
Author(s):  
Florencia Garrido-Charad ◽  
Tomas Vega-Zuniga ◽  
Cristián Gutiérrez-Ibáñez ◽  
Pedro Fernandez ◽  
Luciana López-Jury ◽  
...  
Keyword(s):  
Point Of View ◽  
Stimulus Selection ◽  
Common Input ◽  
Computational Point ◽  
Specific Subset ◽  
Neural Processes ◽  
Neural Tracing ◽  
Input Signals

The optic tectum (TeO), or superior colliculus, is a multisensory midbrain center that organizes spatially orienting responses to relevant stimuli. To define the stimulus with the highest priority at each moment, a network of reciprocal connections between the TeO and the isthmi promotes competition between concurrent tectal inputs. In the avian midbrain, the neurons mediating enhancement and suppression of tectal inputs are located in separate isthmic nuclei, facilitating the analysis of the neural processes that mediate competition. A specific subset of radial neurons in the intermediate tectal layers relay retinal inputs to the isthmi, but at present it is unclear whether separate neurons innervate individual nuclei or a single neural type sends a common input to several of them. In this study, we used in vitro neural tracing and cell-filling experiments in chickens to show that single neurons innervate, via axon collaterals, the three nuclei that comprise the isthmotectal network. This demonstrates that the input signals representing the strength of the incoming stimuli are simultaneously relayed to the mechanisms promoting both enhancement and suppression of the input signals. By performing in vivo recordings in anesthetized chicks, we also show that this common input generates synchrony between both antagonistic mechanisms, demonstrating that activity enhancement and suppression are closely coordinated. From a computational point of view, these results suggest that these tectal neurons constitute integrative nodes that combine inputs from different sources to drive in parallel several concurrent neural processes, each performing complementary functions within the network through different firing patterns and connectivity.

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