A method to predict the impact of point mutations on local structural features

2000 ◽  
Vol 28 (3) ◽  
pp. A78-A78
Author(s):  
S.N. Ruzheinikov ◽  
M.E. Popov ◽  
I.V. Kashparov
Keyword(s):  
Point Mutations ◽  
Structural Features ◽  
The Impact

The Impact of Bioconjugation on the Interfacial Activity of a Protein Biosurfactant

2018 ◽  
Author(s):  
Hossam H Tayeb ◽  
Marina Stienecker ◽  
Anton Middelberg ◽  
Frank Sainsbury
Keyword(s):  
Polyethylene Glycol ◽  
Colloidal Stability ◽  
Point Mutations ◽  
Pharmaceutical Formulations ◽  
Industrial Processes ◽  
Parent Molecule ◽  
Site Specific ◽  
Interfacial Activity ◽  
Surface Active ◽  
The Impact

Biosurfactants, are surface active molecules that can be produced by renewable, industrially scalable biologic processes. DAMP4, a designer biosurfactant, enables the modification of interfaces via genetic or chemical fusion to functional moieties. However, bioconjugation of addressable amines introduces heterogeneity that limits the precision of functionalization as well as the resolution of interfacial characterization. Here we designed DAMP4 variants with cysteine point mutations to allow for site-specific bioconjugation. The DAMP4 variants were shown to retain the structural stability and interfacial activity characteristic of the parent molecule, while permitting efficient and specific conjugation of polyethylene glycol (PEG). PEGylation results in a considerable reduction on the interfacial activity of both single and double mutants. Comparison of conjugates with one or two conjugation sites shows that both the number of conjugates as well as the mass of conjugated material impacts the interfacial activity of DAMP4. As a result, the ability of DAMP4 variants with multiple PEG conjugates to impart colloidal stability on peptide-stabilized emulsions is reduced. We suggest that this is due to constraints on the structure of amphiphilic helices at the interface. Specific and efficient bioconjugation permits the exploration and investigation of the interfacial properties of designer protein biosurfactants with molecular precision. Our findings should therefore inform the design and modification of biosurfactants for their increasing use in industrial processes, and nutritional and pharmaceutical formulations.

scholarly journals Evaluating polymer interplay after hot water pretreatment to investigate maize stem internode recalcitrance

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Amandine Leroy ◽  
Xavier Falourd ◽  
Loïc Foucat ◽  
Valérie Méchin ◽  
Fabienne Guillon ◽  
...  
Keyword(s):  
Cell Wall ◽  
Negative Impact ◽  
Lignin Content ◽  
Structural Features ◽  
Hot Water ◽  
Condensed State ◽  
Structural Factors ◽  
Water Pretreatment ◽  
Hot Water Pretreatment ◽  
The Impact

Abstract Background Biomass recalcitrance is governed by various molecular and structural factors but the interplay between these multiscale factors remains unclear. In this study, hot water pretreatment (HWP) was applied to maize stem internodes to highlight the impact of the ultrastructure of the polymers and their interactions on the accessibility and recalcitrance of the lignocellulosic biomass. The impact of HWP was analysed at different scales, from the polymer ultrastructure or water mobility to the cell wall organisation by combining complementary compositional, spectral and NMR analyses. Results HWP increased the kinetics and yield of saccharification. Chemical characterisation showed that HWP altered cell wall composition with a loss of hemicelluloses (up to 45% in the 40-min HWP) and of ferulic acid cross-linking associated with lignin enrichment. The lignin structure was also altered (up to 35% reduction in β–O–4 bonds), associated with slight depolymerisation/repolymerisation depending on the length of treatment. The increase in $${T}_{1\rho }^{H}$$ T 1 ρ H , $${T}_{HH}$$ T HH and specific surface area (SSA) showed that the cellulose environment was looser after pretreatment. These changes were linked to the increased accessibility of more constrained water to the cellulose in the 5–15 nm pore size range. Conclusion The loss of hemicelluloses and changes in polymer structural features caused by HWP led to reorganisation of the lignocellulose matrix. These modifications increased the SSA and redistributed the water thereby increasing the accessibility of cellulases and enhancing hydrolysis. Interestingly, lignin content did not have a negative impact on enzymatic hydrolysis but a higher lignin condensed state appeared to promote saccharification. The environment and organisation of lignin is thus more important than its concentration in explaining cellulose accessibility. Elucidating the interactions between polymers is the key to understanding LB recalcitrance and to identifying the best severity conditions to optimise HWP in sustainable biorefineries.

scholarly journals Theoretical Studies of the Interaction between Screw Surface and Material in the Mixer

Materials ◽  
2021 ◽  
Vol 14 (4) ◽  
pp. 962
Author(s):  
Andrzej Marczuk ◽  
Vasily Sysuev ◽  
Alexey Aleshkin ◽  
Petr Savinykh ◽  
Nikolay Turubanov ◽  
...  
Keyword(s):  
Friction Coefficient ◽  
High Efficiency ◽  
Animal Feed ◽  
Structural Features ◽  
Power Demand ◽  
Friction Coefficients ◽  
Length Unit ◽  
Mixing Chamber ◽  
Size Of Particles ◽  
The Impact

Mixing is one of the most commonly used processes in food, animal feed, chemical, cosmetic, etc., industries. It is supposed to provide high-quality homogenous, nutritious mixtures. To provide appropriate mixing of materials while maintaining the process high efficiency and low energy consumption it is crucial to explore and describe the material flow caused by the movement of mixing elements and the contact between particles. The process of mixing is also affected by structural features of the machine components and the mixing chamber, speed of mixing, and properties of the mixed materials, such as the size of particles, moisture, friction coefficients. Thus, modeling of the phenomena that accompany the process of mixing using the above-listed parameters is indispensable for appropriate implementation of the process. The paper provides theoretical power calculations that take into account the material speed change, the impact of the material friction coefficient on the screw steel surface and the impact of the friction coefficient on the material, taking into account the loading height of the mixing chamber and the chamber loading value. Dependencies between the mixer power and the product degree of fineness, rotational speed of screw friction coefficients, the number of windings per length unit, and width of the screw tape have been presented on the basis of a developed model. It has been found that power increases along with an increase in the value of these parameters. Verification of the theoretical model indicated consistence of the predicted power demand with the power demand determined in tests performed on a real object for values of the assumed, effective loading, which was 65–75%.

scholarly journals In Planta Mutagenesis Determines the Functional Regions of the Wheat Puroindoline Proteins

Genetics ◽  
2009 ◽  
Vol 183 (3) ◽  
pp. 853-860 ◽  
Author(s):  
Leila Feiz ◽  
Brian S. Beecher ◽  
John M. Martin ◽  
Michael J. Giroux
Keyword(s):  
Functional Analysis ◽  
Allelic Variation ◽  
Screening Method ◽  
Point Mutations ◽  
Missense Mutations ◽  
Grain Hardness ◽  
In Planta ◽  
Rich Region ◽  
Critical Function ◽  
The Impact

In planta analysis of protein function in a crop plant could lead to improvements in understanding protein structure/function relationships as well as selective agronomic or end product quality improvements. The requirements for successful in planta analysis are a high mutation rate, an efficient screening method, and a trait with high heritability. Two ideal targets for functional analysis are the Puroindoline a and Puroindoline b (Pina and Pinb, respectively) genes, which together compose the wheat (Triticum aestivum L.) Ha locus that controls grain texture and many wheat end-use properties. Puroindolines (PINs) together impart soft texture, and mutations in either PIN result in hard seed texture. Studies of the PINs' mode of action are limited by low allelic variation. To create new Pin alleles and identify critical function-determining regions, Pin point mutations were created in planta via EMS treatment of a soft wheat. Grain hardness of 46 unique PIN missense alleles was then measured using segregating F2:F3 populations. The impact of individual missense alleles upon PIN function, as measured by grain hardness, ranged from neutral (74%) to intermediate to function abolishing. The percentage of function-abolishing mutations among mutations occurring in both PINA and PINB was higher for PINB, indicating that PINB is more critical to overall Ha function. This is contrary to expectations in that PINB is not as well conserved as PINA. All function-abolishing mutations resulted from structure-disrupting mutations or from missense mutations occurring near the Tryptophan-rich region. This study demonstrates the feasibility of in planta functional analysis of wheat proteins and that the Tryptophan-rich region is the most important region of both PINA and PINB.

scholarly journals Straight to Low-Sinuosity Drainage Systems in a Variscan-Type Orogen—Constraints from Tectonics, Lithology and Climate

Minerals ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 933
Author(s):  
Harald G. Dill ◽  
Andrei Buzatu ◽  
Sorin-Ionut Balaban
Keyword(s):  
Chemical Weathering ◽  
Current Model ◽  
Drainage System ◽  
Numerical Data ◽  
Structural Features ◽  
Acute Angle ◽  
Drainage Systems ◽  
Starting Point ◽  
Bedrock Lithology ◽  
The Impact

A holistic-modular approach has been taken to study the evolution of three straight to low-sinuosity drainage systems (=SSS) in an uplifted basement block of the Central European Variscides. The development of the SSS is described by means of a quadripartite model. (1) The geological framework of the SSS: Forming the lithological and structural features in the bedrock as a result of different temperature, pressure and dynamic-metamorphic processes. (2) Prestage of SSS: Forming the paleo-landscape with a stable fluvial regime as a starting point for the SSS. (3) Proto-SSS: Transition into the metastable fluvial regime of the SSS. (4) Modern SSS: Operation of the metastable fluvial regime Tectonics plays a dual role. Late Paleozoic fold tectonic creates the basis for the studied SSS and has a guiding effect on the development of morphotectonic units during the Neogene and Quaternary. Late Cenozoic fault tectonics triggered the SSS to incise into the Paleozoic basement. The change in the bedrock lithology has an impact on the fluvial and colluvial sediments as well as their landforms. The latter reflects a conspicuous modification: straight drainage system ⇒ higher sinuosity and paired terraces ⇒ hillwash plains. Climate change has an indirect effect controlling via the bedrock the intensity of mechanical and chemical weathering. The impact on the development of the SSS can be assessed as follows: Tectonics >> climate ≅ bedrock lithology. The three parameters cause a facies zonation: (1) wide-and-shallow valley (Miocene), (2) wide-angle V-shaped valley (Plio-Pleistocene), (3) acute-angle V-shaped valley (Pleistocene), (4) V-shaped to U-shaped valleys (Pleistocene-Holocene). Numerical data relevant for the hydrographic studies of the SSS are determined in each reference area: (1) Quantification of fluvial and colluvial deposits along the drainage system, (2) slope angles, (3) degree of sinuosity as a function of river facies, (4) grain size distribution, (5) grain morphological categorization, (6) grain orientation (“situmetry”), (7) channel density, (8) channel/floodplain ratios. Thermodynamic computations (Eh, pH, concentration of solubles) are made to constrain the paleoclimatic regime during formation of the SSS. The current model of the SSS is restricted in its application to the basement of the Variscan-Type orogens, to an intermediate crustal maturity state.

scholarly journals Effects of Pathological Mutations on the Prion-Like Polymerisation of MyD88

2018 ◽  
Author(s):  
Ailís O’Carroll ◽  
Brieuc Chauvin ◽  
James Brown ◽  
Ava Meagher ◽  
Joanne Coyle ◽  
...  
Keyword(s):  
Single Molecule ◽  
Self Assembly ◽  
Point Mutations ◽  
Adaptor Protein ◽  
Full Length ◽  
Binary Response ◽  
Death Domain ◽  
Tir Domain ◽  
The Impact

AbstractA novel concept has emerged whereby the higher-order self-assembly of proteins provides a simple and robust mechanism for signal amplification. This appears to be a universal signalling mechanism within the innate immune system, where the recognition of pathogens or danger-associated molecular patterns need to trigger a strong, binary response within cells. Previously, multiple structural studies have been limited to single domains, expressed and assembled at high protein concentrations. We therefore set out to develop new in vitro strategies to characterise the behaviour of full-length proteins at physiological levels. In this study we focus on the adaptor protein MyD88, which contains two domains with different self-assembly properties: a TIR domain that can polymerise similarly to the TIR domain of Mal, and a Death Domain that has been shown to oligomerise with helical symmetry in the Myddosome complex. To visualize the behaviour of full-length MyD88 without purification steps, we use single-molecule fluorescence coupled to eukaryotic cell-free protein expression. These experiments demonstrate that at low protein concentration, only full-length MyD88 forms prion-like polymers. We also demonstrate that the metastability of MyD88 polymerisation creates the perfect binary response required in innate signalling: the system is silenced at normal concentrations but upstream signalling creates a “seed” that triggers polymerisation and amplification of the response. These findings pushed us to re-interpret the role of polymerisation in MyD88-related diseases and we studied the impact of disease-associated point mutations L93P, R196C and L252P/L265P at the molecular level. We discovered that all mutations completely block the ability of MyD88 to polymerise. We also confirm that L252P, a gain-of-function mutation, allows the MyD88 mutant to form extremely stable oligomers, even when expressed at low nanomolar concentrations. Thus, our results are consistent with and greatly add to the findings on the Myddosomes digital ‘all-or-none’ responses and the behaviour of the oncogenic mutation of MyD88.

scholarly journals The Impact of Acquired Genetic Abnormalities on the Clinical Translation of Human Pluripotent Stem Cells

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3246
Author(s):  
Alexander Keller ◽  
Claudia Spits
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Chromosomal Abnormalities ◽  
Current Knowledge ◽  
Point Mutations ◽  
Human Pluripotent Stem Cells ◽  
Clinical Translation ◽  
Copy Number Changes ◽  
Clinical Potential ◽  
The Impact

Human pluripotent stem cells (hPSC) are known to acquire chromosomal abnormalities, which range from point mutations to large copy number changes, including full chromosome aneuploidy. These aberrations have a wide-ranging influence on the state of cells, in both the undifferentiated and differentiated state. Currently, very little is known on how these abnormalities will impact the clinical translation of hPSC, and particularly their potential to prime cells for oncogenic transformation. A further complication is that many of these abnormalities exist in a mosaic state in culture, which complicates their detection with conventional karyotyping methods. In this review we discuss current knowledge on how these aberrations influence the cell state and how this may impact the future of research and the cells’ clinical potential.

scholarly journals The effect of ensemble and solo performance on affective experiences induced by music

2016 ◽  
Vol 45 (4) ◽  
pp. 600-608 ◽  
Author(s):  
Carolina Labbé ◽  
Donald Glowinski ◽  
Didier Grandjean
Keyword(s):  
String Quartet ◽  
Positive Emotions ◽  
Musical Training ◽  
Structural Features ◽  
Solo Performance ◽  
Performance Factors ◽  
Affective Experiences ◽  
And Performance ◽  
The Impact ◽  
Instrumental Texture

Scherer and Zentner (2001) propose that affective experiences might be the product of a multiplicative function between structural, performance, listener, and contextual related features. Yet research on the effects of structure, and particularly texture, has mostly focused on perceived emotions. We therefore sought to test the effects of structural features on subjective musical experiences in a listening study by manipulating the performance, solo versus ensemble, of five segments of a piece for string quartet, while also exploring the impact of listener features such as musical training, listening habits and stable dispositions such as empathy. We found that participants ( N = 144, 78% female; Mage = 22.74 years, SD = 5.13) felt like moving more (ME) and perceived their physiological rhythms change more (VE) during ensemble compared to solo conditions. Moreover, ME significantly predicted positive emotions, such as Wonder and Power, while VE significantly predicted both positive and negative emotions, such as Tension and Nostalgia. We also found direct main and interaction effects of both segment and performance factors on all four emotion models. We believe these results support Scherer and Zentner’s model and show the importance of considering the interaction between compositional and instrumental texture when studying music-induced emotions.

QSAR modeling for reaction rate constants of eaq− with diverse organic compounds in water

2020 ◽  
Vol 6 (7) ◽  
pp. 1931-1938
Author(s):  
Shanshan Zheng ◽  
Chao Li ◽  
Gaoliang Wei
Keyword(s):  
Organic Compounds ◽  
Reaction Rate ◽  
Quantitative Structure Activity Relationship ◽  
Structural Features ◽  
Quantitative Structure ◽  
Qsar Modeling ◽  
Reaction Rate Constants ◽  
Structure Activity ◽  
Qsar Models ◽  
The Impact

Two quantitative structure–activity relationship (QSAR) models to predict keaq− of diverse organic compounds were developed and the impact of molecular structural features on eaq− reactivity was investigated.

scholarly journals Quantifying Influences on Intragenomic Mutation Rate

2020 ◽  
Vol 10 (8) ◽  
pp. 2641-2652
Author(s):  
Helmut Simon ◽  
Gavin Huttley
Keyword(s):  
Point Mutations ◽  
Population Based ◽  
Genomic Diversity ◽  
Ensembl Database ◽  
Sequence Context ◽  
The Public ◽  
Recombination Hotspots ◽  
Strand Asymmetry ◽  
The Impact ◽  
Central Base

We report work to quantify the impact on the probability of human genome polymorphism both of recombination and of sequence context at different scales. We use population-based analyses of data on human genetic variants obtained from the public Ensembl database. For recombination, we calculate the variance due to recombination and the probability that a recombination event causes a mutation. We employ novel statistical procedures to take account of the spatial auto-correlation of recombination and mutation rates along the genome. Our results support the view that genomic diversity in recombination hotspots arises largely from a direct effect of recombination on mutation rather than predominantly from the effect of selective sweeps. We also use the statistic of variance due to context to compare the effect on the probability of polymorphism of contexts of various sizes. We find that when the 12 point mutations are considered separately, variance due to context increases significantly as we move from 3-mer to 5-mer and from 5-mer to 7-mer contexts. However, when all mutations are considered in aggregate, these differences are outweighed by the effect of interaction between the central base and its immediate neighbors. This interaction is itself dominated by the transition mutations, including, but not limited to, the CpG effect. We also demonstrate strand-asymmetry of contextual influence in intronic regions, which is hypothesized to be a result of transcription coupled DNA repair. We consider the extent to which the measures we have used can be used to meaningfully compare the relative magnitudes of the impact of recombination and context on mutation.

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