scholarly journals Differential complex formation via paralogs in the human Sin3 protein interaction network

2019 ◽  
Author(s):  
Mark K. Adams ◽  
Charles A.S. Banks ◽  
Janet L. Thornton ◽  
Mihaela E. Sardiu ◽  
Maxime Killer ◽  
...  

ABSTRACTDespite the continued analysis of HDAC inhibitor efficacy in clinical trials, the heterogeneous nature of the protein complexes they target limits our understanding of the beneficial and off-target effects associated with their application. Among the many HDAC protein complexes found within the cell, Sin3 complexes are conserved from yeast to humans and likely play important roles as regulators of transcriptional activity. The functional attributes of these protein complexes remain poorly characterized in humans. Contributing to the poor definition of Sin3 complex attributes in higher eukaryotes is the presence of two Sin3 scaffolding proteins, SIN3A and SIN3B. Here we show that paralog switching influences the interaction networks of the Sin3 complexes. While SIN3A and SIN3B do have unique interaction network components, we find that SIN3A and SIN3B interact with a common set of proteins. Additionally, our results suggest that SIN3A and SIN3B may possess the capacity to form hetero-oligomeric complexes. While one principal form of SIN3B exists in humans, the analysis of rare SIN3B proteoforms provides insight into the domain organization of SIN3B. Together, these findings shed light on the shared and divergent properties of human Sin3 proteins and highlight the heterogeneous nature of the complexes they organize.


2020 ◽  
Vol 19 (9) ◽  
pp. 1468-1484
Author(s):  
Mark K. Adams ◽  
Charles A. S. Banks ◽  
Janet L. Thornton ◽  
Cassandra G. Kempf ◽  
Ying Zhang ◽  
...  

Despite the continued analysis of HDAC inhibitors in clinical trials, the heterogeneous nature of the protein complexes they target limits our understanding of the beneficial and off-target effects associated with their application. Among the many HDAC protein complexes found within the cell, Sin3 complexes are conserved from yeast to humans and likely play important roles as regulators of transcriptional activity. The presence of two Sin3 paralogs in humans, SIN3A and SIN3B, may result in a heterogeneous population of Sin3 complexes and contributes to our poor understanding of the functional attributes of these complexes. Here, we profile the interaction networks of SIN3A and SIN3B to gain insight into complex composition and organization. In accordance with existing data, we show that Sin3 paralog identity influences complex composition. Additionally, chemical cross-linking MS identifies domains that mediate interactions between Sin3 proteins and binding partners. The characterization of rare SIN3B proteoforms provides additional evidence for the existence of conserved and divergent elements within human Sin3 proteins. Together, these findings shed light on both the shared and divergent properties of human Sin3 proteins and highlight the heterogeneous nature of the complexes they organize.



2013 ◽  
Vol 42 (4) ◽  
pp. 3-9
Author(s):  
Armin Geertz

This introduction to the special issue on narrative discusses various ways of approaching religious narrative. It looks at various evolutionary hypotheses and distinguishes between three fundamental aspects of narrative: 1. the neurobiological, psychological, social and cultural mechanisms and processes, 2. the many media and methods used in human communication, and 3. the variety of expressive genres. The introduction ends with a definition of narrative.



Sexualities ◽  
2020 ◽  
pp. 136346072098169
Author(s):  
Aidan McKearney

This article focuses on the experiences of gay men in the rural west and northwest region of Ireland, during a period of transformational social and political change in Irish society. These changes have helped facilitate new forms of LGBTQI visibility, and local radicalism in the region. Same-sex weddings, establishment of rural LGBT groups and marching under an LGBT banner at St Patricks Day parades would have been unthinkable in the recent past; but they are now becoming a reality. The men report continuing challenges in their lives as gay men in the nonmetropolitan space, but the emergence of new visibility, voice and cultural acceptance of LGBT people is helping change their lived experiences. The study demonstrates the impact of local activist LGBT citizens. Through their testimonies we can gain an insight into the many, varied and interwoven factors that have interplayed to create the conditions necessary for the men to: increasingly define themselves as gay to greater numbers of people in their localities; to embrace greater visibility and eschew strategies of silence; and aspire to a host of legal, political, cultural and social rights including same-sex marriage. Organic forms of visibility and local radicalism have emerged in the region and through an analysis of their testimonies we can see how the men continue to be transformed by an ever-changing landscape.



2021 ◽  
Vol 7 ◽  
pp. 237802312110244
Author(s):  
Katrin Auspurg ◽  
Josef Brüderl

In 2018, Silberzahn, Uhlmann, Nosek, and colleagues published an article in which 29 teams analyzed the same research question with the same data: Are soccer referees more likely to give red cards to players with dark skin tone than light skin tone? The results obtained by the teams differed extensively. Many concluded from this widely noted exercise that the social sciences are not rigorous enough to provide definitive answers. In this article, we investigate why results diverged so much. We argue that the main reason was an unclear research question: Teams differed in their interpretation of the research question and therefore used diverse research designs and model specifications. We show by reanalyzing the data that with a clear research question, a precise definition of the parameter of interest, and theory-guided causal reasoning, results vary only within a narrow range. The broad conclusion of our reanalysis is that social science research needs to be more precise in its “estimands” to become credible.



2021 ◽  
Vol 11 (2) ◽  
Author(s):  
María Jiménez-Buedo

AbstractReactivity, or the phenomenon by which subjects tend to modify their behavior in virtue of their being studied upon, is often cited as one of the most important difficulties involved in social scientific experiments, and yet, there is to date a persistent conceptual muddle when dealing with the many dimensions of reactivity. This paper offers a conceptual framework for reactivity that draws on an interventionist approach to causality. The framework allows us to offer an unambiguous definition of reactivity and distinguishes it from placebo effects. Further, it allows us to distinguish between benign and malignant forms of the phenomenon, depending on whether reactivity constitutes a danger to the validity of the causal inferences drawn from experimental data.



Author(s):  
Rohan Dandage ◽  
Caroline M Berger ◽  
Isabelle Gagnon-Arsenault ◽  
Kyung-Mee Moon ◽  
Richard Greg Stacey ◽  
...  

Abstract Hybrids between species often show extreme phenotypes, including some that take place at the molecular level. In this study, we investigated the phenotypes of an interspecies diploid hybrid in terms of protein-protein interactions inferred from protein correlation profiling. We used two yeast species, Saccharomyces cerevisiae and Saccharomyces uvarum, which are interfertile, but yet have proteins diverged enough to be differentiated using mass spectrometry. Most of the protein-protein interactions are similar between hybrid and parents, and are consistent with the assembly of chimeric complexes, which we validated using an orthogonal approach for the prefoldin complex. We also identified instances of altered protein-protein interactions in the hybrid, for instance in complexes related to proteostasis and in mitochondrial protein complexes. Overall, this study uncovers the likely frequent occurrence of chimeric protein complexes with few exceptions, which may result from incompatibilities or imbalances between the parental proteins.



2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Haomiao Cheng ◽  
Zhanru Shao ◽  
Chang Lu ◽  
Delin Duan

Abstract Background The nitrogen-containing polysaccharide chitin is the second most abundant biopolymer on earth and is found in the cell walls of diatoms, where it serves as a scaffold for biosilica deposition. Diatom chitin is an important source of carbon and nitrogen in the marine environment, but surprisingly little is known about basic chitinase metabolism in diatoms. Results Here, we identify and fully characterize 24 chitinase genes from the model centric diatom Thalassiosira pseudonana. We demonstrate that their expression is broadly upregulated under abiotic stresses, despite the fact that chitinase activity itself remains unchanged, and we discuss several explanations for this result. We also examine the potential transcriptional complexity of the intron-rich T. pseudonana chitinase genes and provide evidence for two separate tandem duplication events during their evolution. Conclusions Given the many applications of chitin and chitin derivatives in suture production, wound healing, drug delivery, and other processes, new insight into diatom chitin metabolism has both theoretical and practical value.



Author(s):  
Marian Sikora ◽  
Janusz Gołdasz

The aim of this work is to provide an insight into the rattle noise phenomena occurring in double-tube (twin-tube) vehicle suspension dampers. In the dampers the particular phenomenon results from interactions between the valve(s) and the fluid passing through them. The rattling noise phenomena is known to degrade the vehicle passenger’s perception of ride comfort as well as to influence the performance of the dampers at low and medium speeds in particular. In the paper the authors reveal the results of a DOE (Design of Experiment) study involving several design parameters known to affect rattling occurrence. By running a series of purpose-designed tests the authors investigate not only the contribution of each particular parameter but the interactions between them. The results are presented in the form of pareto charts, main effect plots as well as interaction plots. It is expected the outcome of the analysis will aid in a better comprehension of the phenomena as well the definition of valve configurations to minimize their performance degradation.



2020 ◽  
Vol 1 (1) ◽  
pp. 57-64
Author(s):  
Jonathan Fighel

Security is multidimensional in nature and diverse in practice. This diversity leads to difficulty in providing a single all-encompassing definition for the many applied domains of security. Security cannot be considered singular in concept definition, as definition is dependent on applied context. Security incorporates diverse and multi-disciplined actors, originating and practicing across many disciplines. This multidimensional nature of security results unclear understanding of a definition for the concept of security. Bridging the gap between the traditional definitions of science and the undefined definition of what is Security can be achieved through Scientific Security Research methodologies that will be engaged and implemented in the exploration, analysis and conclusions of the systematic and organized body of knowledge.



2021 ◽  
Vol 23 (2) ◽  
pp. 34-37
Author(s):  
Thomas J. Beck

ProQuest Historical Newspapers: Leftist Newspapers and Periodicals is a source for leftist publications (mostly newspapers), largely published in the twentieth century. Here, the user can access articles in PDF format from 156 national and international publications. Navigating this database and the documents therein can be easily done, but articles cannot be magnified or reduced, which may prove problematic with PDFs of old newspapers. Database content can be found through browsing or by using a basic and/or advanced search. The browse and basic search options here are understandable, but the advanced search is not self-explanatory and can possibly confuse the user. As a consequence, a new user of this database will probably benefit from instruction in its use from either the vendor or someone else familiar with this resource. However, when this search function is used properly it can produce numerous, on-point results for any query. The same is true of the basic search and browsing features, though they tend to produce larger lists of results that are less on-point than the advanced search. The vendor did not provide specific price information for this review, only indicating that pricing is determined by an institution's size and number of users. As this provides potential subscribers with very little insight into the cost of acquiring this resource, its advised that they contact ProQuest for a price quote tailored to their own institution. Its licensing agreement is the same as those used for all ProQuest databases and is average in its composition (though somewhat longer than average). The quality and quantity of content in this resource is notable, and it will certainly be of use to those looking for articles from leftist newspapers and periodicals. However, the definition of “leftist” here may be problematic for some users! Communist and Socialist publications are certainly available in this database, but those for Anarchists, Social Democrats, and other leftists are not.



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