scholarly journals The Hitchhiker's guide to glycoproteomics

Author(s):  
Tiago Oliveira ◽  
Morten Thaysen-Andersen ◽  
Nicolle H. Packer ◽  
Daniel Kolarich

Protein glycosylation is one of the most common post-translational modifications that are essential for cell function across all domains of life. Changes in glycosylation are considered a hallmark of many diseases, thus making glycoproteins important diagnostic and prognostic biomarker candidates and therapeutic targets. Glycoproteomics, the study of glycans and their carrier proteins in a system-wide context, is becoming a powerful tool in glycobiology that enables the functional analysis of protein glycosylation. This ‘Hitchhiker's guide to glycoproteomics’ is intended as a starting point for anyone who wants to explore the emerging world of glycoproteomics. The review moves from the techniques that have been developed for the characterisation of single glycoproteins to technologies that may be used for a successful complex glycoproteome characterisation. Examples of the variety of approaches, methodologies, and technologies currently used in the field are given. This review introduces the common strategies to capture glycoprotein-specific and system-wide glycoproteome data from tissues, body fluids, or cells, and a perspective on how integration into a multi-omics workflow enables a deep identification and characterisation of glycoproteins — a class of biomolecules essential in regulating cell function.

2021 ◽  
Author(s):  
Nakita Buenbrazo

Protein glycosylation is the most abundant and diverse protein modification that occurs in all domains of life. It is defined as the covalent attachment of a carbohydrate moiety to a specific amino acid on a target protein. The functional role of this attachment is implicated in and spans various cell processes from cell signaling, cell defense, and pathogenesis – to name a few. A specific type of protein glycosylation, called protein O-mannosylation (POM) is a process found to be conserved from bacteria to man. In humans, POM is required for healthy cell function, and the absence of POM can cause fatal diseases. Certain prokaryotic species possess a related POM system, but it is poorly understood. It is our hypothesis that the analysis of the POM system in simpler organisms can aid in the characterization of this process and the functional role of the mannosylated proteins that are produced. However, the protocols to prove this theory do not yet exist. This thesis establishes a collection of developed protocols that can be used to characterize the POM systems from gram-positive species Corynebacterium glutamicum and Cellulomonas fimi. In addition the first ever evidence of a C. fimi glycoprotein being glycosylated by the endogenous C. glutamicum POM system is provided.


2021 ◽  
Author(s):  
Nakita Buenbrazo

Protein glycosylation is the most abundant and diverse protein modification that occurs in all domains of life. It is defined as the covalent attachment of a carbohydrate moiety to a specific amino acid on a target protein. The functional role of this attachment is implicated in and spans various cell processes from cell signaling, cell defense, and pathogenesis – to name a few. A specific type of protein glycosylation, called protein O-mannosylation (POM) is a process found to be conserved from bacteria to man. In humans, POM is required for healthy cell function, and the absence of POM can cause fatal diseases. Certain prokaryotic species possess a related POM system, but it is poorly understood. It is our hypothesis that the analysis of the POM system in simpler organisms can aid in the characterization of this process and the functional role of the mannosylated proteins that are produced. However, the protocols to prove this theory do not yet exist. This thesis establishes a collection of developed protocols that can be used to characterize the POM systems from gram-positive species Corynebacterium glutamicum and Cellulomonas fimi. In addition the first ever evidence of a C. fimi glycoprotein being glycosylated by the endogenous C. glutamicum POM system is provided.


2020 ◽  
Vol 64 (1) ◽  
pp. 135-153 ◽  
Author(s):  
Lauren Elizabeth Smith ◽  
Adelina Rogowska-Wrzesinska

Abstract Post-translational modifications (PTMs) are integral to the regulation of protein function, characterising their role in this process is vital to understanding how cells work in both healthy and diseased states. Mass spectrometry (MS) facilitates the mass determination and sequencing of peptides, and thereby also the detection of site-specific PTMs. However, numerous challenges in this field continue to persist. The diverse chemical properties, low abundance, labile nature and instability of many PTMs, in combination with the more practical issues of compatibility with MS and bioinformatics challenges, contribute to the arduous nature of their analysis. In this review, we present an overview of the established MS-based approaches for analysing PTMs and the common complications associated with their investigation, including examples of specific challenges focusing on phosphorylation, lysine acetylation and redox modifications.


2015 ◽  
Vol 60 (1) ◽  
pp. 81-102
Author(s):  
KErstin Thomas

Kerstin Thomas revaluates the famous dispute between Martin Heidegger, Meyer Schapiro, and Jacques Derrida, concerning a painting of shoes by Vincent Van Gogh. The starting point for this dispute was the description and analysis of things and artworks developed in his essay, “The Origin of the Work of Art”. In discussing Heidegger’s account, the art historian Meyer Schapiro’s main point of critique concerned Heidegger’s claim that the artwork reveals the truth of equipment in depicting shoes of a peasant woman and thereby showing her world. Schapiro sees a striking paradox in Heidegger’s claim for truth, based on a specific object in a specific artwork while at the same time following a rather metaphysical idea of the artwork. Kerstin Thomas proposes an interpretation, which exceeds the common confrontation of philosophy versus art history by focussing on the respective notion of facticity at stake in the theoretical accounts of both thinkers. Schapiro accuses Heidegger of a lack of concreteness, which he sees as the basis for every truth claim on objects. Thomas understands Schapiro’s objections as motivated by this demand for a facticity, which not only includes the work of art, but also investigator in his concrete historical perspective. Truth claims under such conditions of facticity are always relative to historical knowledge, and open to critical intervention and therefore necessarily contingent. Following Thomas, Schapiro’s critique shows that despite his intention of giving the work of art back its autonomy, Heidegger could be accused of achieving quite the opposite: through the abstraction of the concrete, the factual, and the given to the type, he actually sets the self and the realm of knowledge of the creator as absolute and not the object of his knowledge. Instead, she argues for a revaluation of Schapiro’s position with recognition of the arbitrariness of the artwork, by introducing the notion of factuality as formulated by Quentin Meillassoux. Understood as exchange between artist and object in its concrete material quality as well as with the beholder, the truth of painting could only be shown as radically contingent. Thomas argues that the critical intervention of Derrida who discusses both positions anew is exactly motivated by a recognition of the contingent character of object, artwork and interpretation. His deconstructive analysis can be understood as recognition of the dynamic character of things and hence this could be shown with Meillassoux to be exactly its character of facticity – or factuality.


2018 ◽  
Vol 22 (78) ◽  
pp. 63-74
Author(s):  
Janne Lindqvist

Our understanding of Aristotle’s Rhetoric is still incomplete and distorted. This is especially true concerning his analysis of the specific topics of pathos that make up a significant part of the second book of the text. Even though this part of the text is almost twice as long as the analysis of the common topics, the discussion has attracted surprisingly small scholarly interest, at least as viewed as an example of a list of topics, as the researchers that have aspired to an understanding of “the topics” as such have almost all ignored this part of the text. The purpose of this essay is to lay out the grounds for such a study. The result of the essay is firstly a distinction between two kinds of specific topics, here somewhat ponderously labeled schematic and concrete specific topics. With these as a starting point it is possible to make a further distinction between three general specific topics here named subject, stimulus and agent. These three schematic topics could, it is finally suggested, be as useful in the 21:st century as they were in an Athens of the 4th century BCE


2021 ◽  
Vol 12 (2) ◽  
pp. 116-145
Author(s):  
Paula Giliker

Abstract In this paper, I will examine the extent to which the common law of tort in England and Wales imposes a duty to prevent harm on public authorities and private individuals. As will be seen, the starting point for the common law is that such liability should, in both cases, be regarded as exceptional. This must, however, be weighed against duties to prevent harm that arise under the torts of negligence and breach of statutory duty. Public authorities may also face claims that their failure to prevent harm is in breach of ECHR arts 2 or 3. While the law is complex, this paper identifies three key arguments that explain the current legal position at common law, namely that: (i) tort law should treat private and public parties alike: (ii) human rights claims should be treated as distinct from private law claims and (iii) libertarian concerns signify that a duty to prevent harm should be exceptional and needs to be justified. While these arguments provide both an explanation of and a justification for the current law, this article questions to what extent the treatment of public authority liability may be regarded as unduly harsh on vulnerable claimants.


Utilitas ◽  
1990 ◽  
Vol 2 (2) ◽  
pp. 245-266 ◽  
Author(s):  
P. J. Kelly

The argument of this paper is part of a general defence of the claim that Bentham's moral theory embodies a utilitarian theory of distributive justice, which is developed in his Civil Law writings. Whereas it is a commonplace of recent revisionist scholarship to argue that J. S. Mill had a developed utilitarian theory of justice, few scholars regard Bentham as having a theory of justice, let alone one that rivals in sophistication that of Mill. Indeed, Gerald J. Postema in his bookBentham and the Common Law Tradition, argues that Bentham had no substantial concern with the concept of justice, and that what analysis of the concept there is in Bentham's thought is unlike the utilitarian theory of justice to be found in chapter five of J. S. Mill'sUtilitarianismAlthough Postema's interpretation is not the only one that will be addressed in this paper, it serves as an important starting point for any rival interpretation of Bentham's ethical theory for two reasons. Firstly, it is the most comprehensive and most penetrating discussion of Bentham's utilitarian theory, drawing as it does on a wide variety of published and unpublished materials written throughout Bentham's career. Secondly, it is interesting in this particular context because the contrast that Postema draws between Bentham's and Mill's theories of justice depends upon a particular reading of Mill's theory of justice and utility which is derived from recent scholarship and which is by no means uncontroversial. As part of the defence of the claim that Bentham had a sophisticated theory of distributive justice, it will be argued in this paper that the contrast drawn between Bentham and Mill does not stand up to careful scrutiny, for insofar as Mill's theory of justice can be consistently defended it is not significantly different from the utilitarian strategy that Bentham employed for incorporating considerations of distributive justice within his theory. This is not to claim that there are not significant differences between the theories of justice of Bentham and J. S. Mill, but it is to claim that whatever technical differences exist between their theories, both writers saw the need to incorporate the concept of justice within utilitarianism. Therefore, rather than showing that Mill is an interesting thinker to the extent that he abandons his early Benthamism, by demonstrating how close Mill's theory of utility and justice is to that of Bentham, it will be possible to argue that Bentham employed a sophisticated and subtle utilitarian theory that was responsive to the sort of problems which occupied Mill a generation later.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Xinjin Chen ◽  
Bolin Fan ◽  
Chenlong Fan ◽  
Zhongliang Wang ◽  
Eakapol Wangkahart ◽  
...  

Abstract Backgroud Streptococcus agalactiae is a common colonizer of the rectovaginal tract and lead to infectious diseases of neonatal and non-pregnant adults, which also causes infectious disease in fish and a zoonotic risk as well. Lysine crotonylation (Kcr) is a kind of histone post-translational modifications discovered in 2011. In yeast and mammals, Kcr function as potential enhancers and promote gene expression. However, lysine crotonylation in S. agalactiae has not been studied yet. Methods In this study, the crotonylation profiling of fish pathogen, S. agalactiae was investigated by combining affinity enrichment with LC MS/MS. The Kcr modification of several selected proteins were further validated by Western blotting. Results In the present study, we conducted the proteome-wide profiling of Kcr in S. agalactiae and identified 241 Kcr sites from 675 screened proteins for the first time. Bioinformatics analysis showed that 164 sequences were matched to a total of six definitively conserved motifs, and many of them were significantly enriched in metabolic processes, cellular process, and single-organism processes. Moreover, four crotonylation modified proteins were predicted as virulence factors or to being part of the quorum sensing system PTMs on bacteria. The data are available via ProteomeXchange with identifier PXD026445. Conclusions These data provide a promising starting point for further functional research of crotonylation in bacterial virulence in S. agalactiae.


2018 ◽  
Vol 29 (4) ◽  
pp. 533-544
Author(s):  
Marija Velinov

This paper argues that there is continuity in Foucault?s thought, as opposed to the common division of his work into three phases, each marking a distinct field of research - discourse, power, subject. The idea is that there are no radical turns in his work that justify this division; rather, there is a shift of focus: all crucial concepts are present (more or less [in]explicitly) in all periods of his thought and in all of his undoubtedly differently-toned and oriented works. This is shown through examining the characteristics of archaeology and genealogy, their relation, as well as the relation of discursive practices and strategies of power to knowledge. The retrospective and (re)interpretation intend to shed light on the constant interplay between concepts that demonstrate continuity in Foucault?s thought. The viewpoint, based in the integrity of Foucault?s work, offers a better starting point for understanding certain aspects of his theories.


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