scholarly journals Protein Semisynthesis Provides Access to Tau Disease-Associated Post-translational Modifications (PTMs) and Paves the Way to Deciphering the Tau PTM Code in Health and Diseased States

2018 ◽  
Vol 140 (21) ◽  
pp. 6611-6621 ◽  
Author(s):  
Mahmood Haj-Yahya ◽  
Hilal A. Lashuel
Keyword(s):  
Post Translational Modifications ◽  
Protein Semisynthesis ◽  
The Way

scholarly journals An Engineered Version of Human PON2 Opens the Way to Understand the Role of Its Post-Translational Modifications in Modulating Catalytic Activity

PLoS ONE ◽  
2015 ◽  
Vol 10 (12) ◽  
pp. e0144579 ◽  
Author(s):  
Luigi Mandrich ◽  
Mariangela Cerreta ◽  
Giuseppe Manco
Keyword(s):  
Catalytic Activity ◽  
Post Translational Modifications ◽  
The Way

scholarly journals Elucidating the Role of C-Terminal Post-Translational Modifications Using Protein Semisynthesis Strategies: α-Synuclein Phosphorylation at Tyrosine 125

2012 ◽  
Vol 134 (11) ◽  
pp. 5196-5210 ◽  
Author(s):  
Mirva Hejjaoui ◽  
Sara Butterfield ◽  
Bruno Fauvet ◽  
Filip Vercruysse ◽  
Jia Cui ◽  
...  
Keyword(s):  
Post Translational Modifications ◽  
Protein Semisynthesis

Consequences of post-translational modifications on amyloid proteins as revealed by protein semisynthesis

2021 ◽  
Vol 64 ◽  
pp. 76-89
Author(s):  
Stuart P. Moon ◽  
Aaron T. Balana ◽  
Matthew R. Pratt
Keyword(s):  
Amyloid Proteins ◽  
Post Translational Modifications ◽  
Protein Semisynthesis

Packaging development: how chromatin controls transcription in zebrafish embryogenesis

2019 ◽  
Vol 47 (2) ◽  
pp. 713-724 ◽  
Author(s):  
Julia A. Horsfield
Keyword(s):  
Gene Expression ◽  
Developmental Biology ◽  
Histone Variants ◽  
Transgenerational Inheritance ◽  
Developmental Gene ◽  
Post Translational Modifications ◽  
Developmental Gene Expression ◽  
Similarities And Differences ◽  
Zebrafish Embryogenesis ◽  
The Way

Abstract How developmental gene expression is activated, co-ordinated and maintained is one of the biggest questions in developmental biology. While transcription factors lead the way in directing developmental gene expression, their accessibility to the correct repertoire of genes can depend on other factors such as DNA methylation, the presence of particular histone variants and post-translational modifications of histones. Collectively, factors that modify DNA or affect its packaging and accessibility contribute to a chromatin landscape that helps to control the timely expression of developmental genes. Zebrafish, perhaps better known for their strength as a model of embryology and organogenesis during development, are coming to the fore as a powerful model for interpreting the role played by chromatin in gene expression. Several recent advances have shown that zebrafish exhibit both similarities and differences to other models (and humans) in the way that they employ chromatin mechanisms of gene regulation. Here, I review how chromatin influences developmental transcriptional programmes during early zebrafish development, patterning and organogenesis. Lastly, I briefly highlight the importance of zebrafish chromatin research towards the understanding of human disease and transgenerational inheritance.

Self-sacrifice for in-group's history: A diachronic perspective

2018 ◽  
Vol 41 ◽  
Author(s):  
Maria Babińska ◽  
Michal Bilewicz
Keyword(s):  
Clinical Psychology ◽  
Historical Events ◽  
Emotional Events ◽  
Reciprocal Process ◽  
The Way

AbstractThe problem of extended fusion and identification can be approached from a diachronic perspective. Based on our own research, as well as findings from the fields of social, political, and clinical psychology, we argue that the way contemporary emotional events shape local fusion is similar to the way in which historical experiences shape extended fusion. We propose a reciprocal process in which historical events shape contemporary identities, whereas contemporary identities shape interpretations of past traumas.

What is the purpose of cognition?

2020 ◽  
Vol 43 ◽  
Author(s):  
Aba Szollosi ◽  
Ben R. Newell
Keyword(s):  
Infinite Number ◽  
Human Cognition ◽  
The Way

Abstract The purpose of human cognition depends on the problem people try to solve. Defining the purpose is difficult, because people seem capable of representing problems in an infinite number of ways. The way in which the function of cognition develops needs to be central to our theories.

Peculiarity Parameters

1976 ◽  
Vol 32 ◽  
pp. 233-254
Author(s):  
H. M. Maitzen
Keyword(s):  
Magnetic Field ◽  
Magnetic Fields ◽  
Theoretical Work ◽  
Observational Evidence ◽  
Rotator Model ◽  
Peculiar Behaviour ◽  
Field Spectrum ◽  
Oblique Rotator ◽  
Ap Stars ◽  
The Way

Ap stars are peculiar in many aspects. During this century astronomers have been trying to collect data about these and have found a confusing variety of peculiar behaviour even from star to star that Struve stated in 1942 that at least we know that these phenomena are not supernatural. A real push to start deeper theoretical work on Ap stars was given by an additional observational evidence, namely the discovery of magnetic fields on these stars by Babcock (1947). This originated the concept that magnetic fields are the cause for spectroscopic and photometric peculiarities. Great leaps for the astronomical mankind were the Oblique Rotator model by Stibbs (1950) and Deutsch (1954), which by the way provided mathematical tools for the later handling pulsar geometries, anti the discovery of phase coincidence of the extrema of magnetic field, spectrum and photometric variations (e.g. Jarzebowski, 1960).

The mensuration of interfaces

1992 ◽  
Vol 50 (1) ◽  
pp. 216-217
Author(s):  
W.M. Stobbs
Keyword(s):  
Electron Microscopy ◽  
50Th Anniversary ◽  
Numerical Data ◽  
Industrial Applications ◽  
Dynamical Theory ◽  
Large Strains ◽  
Reasonable Approach ◽  
Lattice Resolution ◽  
Analogue To Digital ◽  
The Way

I do not have access to the abstracts of the first meeting of EMSA but at this, the 50th Anniversary meeting of the Electron Microscopy Society of America, I have an excuse to consider the historical origins of the approaches we take to the use of electron microscopy for the characterisation of materials. I have myself been actively involved in the use of TEM for the characterisation of heterogeneities for little more than half of that period. My own view is that it was between the 3rd International Meeting at London, and the 1956 Stockholm meeting, the first of the European series , that the foundations of the approaches we now take to the characterisation of a material using the TEM were laid down. (This was 10 years before I took dynamical theory to be etched in stone.) It was at the 1956 meeting that Menter showed lattice resolution images of sodium faujasite and Hirsch, Home and Whelan showed images of dislocations in the XlVth session on “metallography and other industrial applications”. I have always incidentally been delighted by the way the latter authors misinterpreted astonishingly clear thickness fringes in a beaten (”) foil of Al as being contrast due to “large strains”, an error which they corrected with admirable rapidity as the theory developed. At the London meeting the research described covered a broad range of approaches, including many that are only now being rediscovered as worth further effort: however such is the power of “the image” to persuade that the above two papers set trends which influence, perhaps too strongly, the approaches we take now. Menter was clear that the way the planes in his image tended to be curved was associated with the imaging conditions rather than with lattice strains, and yet it now seems to be common practice to assume that the dots in an “atomic resolution image” can faithfully represent the variations in atomic spacing at a localised defect. Even when the more reasonable approach is taken of matching the image details with a computed simulation for an assumed model, the non-uniqueness of the interpreted fit seems to be rather rarely appreciated. Hirsch et al., on the other hand, made a point of using their images to get numerical data on characteristics of the specimen they examined, such as its dislocation density, which would not be expected to be influenced by uncertainties in the contrast. Nonetheless the trends were set with microscope manufacturers producing higher and higher resolution microscopes, while the blind faith of the users in the image produced as being a near directly interpretable representation of reality seems to have increased rather than been generally questioned. But if we want to test structural models we need numbers and it is the analogue to digital conversion of the information in the image which is required.

Reading the phosphorylation code: binding of the 14-3-3 protein to multivalent client phosphoproteins

2020 ◽  
Vol 477 (7) ◽  
pp. 1219-1225 ◽  
Author(s):  
Nikolai N. Sluchanko
Keyword(s):  
Protein Function ◽  
Intrinsically Disordered Protein ◽  
Structural Basis ◽  
Major Protein ◽  
Post Translational Modifications ◽  
Protein Protein Interaction ◽  
Intrinsically Disordered ◽  
Biochemical Journal ◽  
Multiple Binding ◽  
And Control

Many major protein–protein interaction networks are maintained by ‘hub’ proteins with multiple binding partners, where interactions are often facilitated by intrinsically disordered protein regions that undergo post-translational modifications, such as phosphorylation. Phosphorylation can directly affect protein function and control recognition by proteins that ‘read’ the phosphorylation code, re-wiring the interactome. The eukaryotic 14-3-3 proteins recognizing multiple phosphoproteins nicely exemplify these concepts. Although recent studies established the biochemical and structural basis for the interaction of the 14-3-3 dimers with several phosphorylated clients, understanding their assembly with partners phosphorylated at multiple sites represents a challenge. Suboptimal sequence context around the phosphorylated residue may reduce binding affinity, resulting in quantitative differences for distinct phosphorylation sites, making hierarchy and priority in their binding rather uncertain. Recently, Stevers et al. [Biochemical Journal (2017) 474: 1273–1287] undertook a remarkable attempt to untangle the mechanism of 14-3-3 dimer binding to leucine-rich repeat kinase 2 (LRRK2) that contains multiple candidate 14-3-3-binding sites and is mutated in Parkinson's disease. By using the protein-peptide binding approach, the authors systematically analyzed affinities for a set of LRRK2 phosphopeptides, alone or in combination, to a 14-3-3 protein and determined crystal structures for 14-3-3 complexes with selected phosphopeptides. This study addresses a long-standing question in the 14-3-3 biology, unearthing a range of important details that are relevant for understanding binding mechanisms of other polyvalent proteins.

Dicarbonyl derived post-translational modifications: chemistry bridging biology and aging-related disease

2020 ◽  
Vol 64 (1) ◽  
pp. 97-110
Author(s):  
Christian Sibbersen ◽  
Mogens Johannsen
Keyword(s):  
Mass Spectrometry ◽  
Future Research ◽  
Amino Acid Residues ◽  
Post Translational Modification ◽  
Dicarbonyl Compounds ◽  
Protein Targets ◽  
Post Translational Modifications ◽  
Reactive Protein ◽  
Glycation End Products ◽  
Direct Mass Spectrometry

Abstract In living systems, nucleophilic amino acid residues are prone to non-enzymatic post-translational modification by electrophiles. α-Dicarbonyl compounds are a special type of electrophiles that can react irreversibly with lysine, arginine, and cysteine residues via complex mechanisms to form post-translational modifications known as advanced glycation end-products (AGEs). Glyoxal, methylglyoxal, and 3-deoxyglucosone are the major endogenous dicarbonyls, with methylglyoxal being the most well-studied. There are several routes that lead to the formation of dicarbonyl compounds, most originating from glucose and glucose metabolism, such as the non-enzymatic decomposition of glycolytic intermediates and fructosyl amines. Although dicarbonyls are removed continuously mainly via the glyoxalase system, several conditions lead to an increase in dicarbonyl concentration and thereby AGE formation. AGEs have been implicated in diabetes and aging-related diseases, and for this reason the elucidation of their structure as well as protein targets is of great interest. Though the dicarbonyls and reactive protein side chains are of relatively simple nature, the structures of the adducts as well as their mechanism of formation are not that trivial. Furthermore, detection of sites of modification can be demanding and current best practices rely on either direct mass spectrometry or various methods of enrichment based on antibodies or click chemistry followed by mass spectrometry. Future research into the structure of these adducts and protein targets of dicarbonyl compounds may improve the understanding of how the mechanisms of diabetes and aging-related physiological damage occur.

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