scholarly journals Yeast R2TP Interacts with Extended Termini of Client Protein Nop58p

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Ge Yu ◽  
Yu Zhao ◽  
Shaoxiong Tian ◽  
Jay Rai ◽  
Huan He ◽  
...  
Keyword(s):  
Molecular Basis ◽  
Maltose Binding Protein ◽  
Small Subunit ◽  
General Mechanism ◽  
Yeast Genetics ◽  
Client Protein ◽  
Present Evidence ◽  
Aaa Atpase ◽  
The Core

AbstractThe AAA + ATPase R2TP complex facilitates assembly of a number of ribonucleoprotein particles (RNPs). Although the architecture of R2TP is known, its molecular basis for acting upon multiple RNPs remains unknown. In yeast, the core subunit of the box C/D small nucleolar RNPs, Nop58p, is the target for R2TP function. In the recently observed U3 box C/D snoRNP as part of the 90 S small subunit processome, the unfolded regions of Nop58p are observed to form extensive interactions, suggesting a possible role of R2TP in stabilizing the unfolded region of Nop58p prior to its assembly. Here, we analyze the interaction between R2TP and a Maltose Binding Protein (MBP)-fused Nop58p by biophysical and yeast genetics methods. We present evidence that R2TP interacts largely with the unfolded termini of Nop58p. Our results suggest a general mechanism for R2TP to impart specificity by recognizing unfolded regions in its clients.

scholarly journals Hrr25 triggers selective autophagy–related pathways by phosphorylating receptor proteins

2014 ◽  
Vol 207 (1) ◽  
pp. 91-105 ◽  
Author(s):  
Chikara Tanaka ◽  
Li-Jing Tan ◽  
Keisuke Mochida ◽  
Hiromi Kirisako ◽  
Michiko Koizumi ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Molecular Basis ◽  
Receptor Proteins ◽  
Selective Autophagy ◽  
The Core ◽  
The Common ◽  
Related Proteins

In selective autophagy, degradation targets are specifically recognized, sequestered by the autophagosome, and transported into the lysosome or vacuole. Previous studies delineated the molecular basis by which the autophagy machinery recognizes those targets, but the regulation of this process is still poorly understood. In this paper, we find that the highly conserved multifunctional kinase Hrr25 regulates two distinct selective autophagy–related pathways in Saccharomyces cerevisiae. Hrr25 is responsible for the phosphorylation of two receptor proteins: Atg19, which recognizes the assembly of vacuolar enzymes in the cytoplasm-to-vacuole targeting pathway, and Atg36, which recognizes superfluous peroxisomes in pexophagy. Hrr25-mediated phosphorylation enhances the interactions of these receptors with the common adaptor Atg11, which recruits the core autophagy-related proteins that mediate the formation of the autophagosomal membrane. Thus, this study introduces regulation of selective autophagy as a new role of Hrr25 and, together with other recent studies, reveals that different selective autophagy–related pathways are regulated by a uniform mechanism: phosphoregulation of the receptor–adaptor interaction.

Does a Ribosome Really Read? On the Cognitive Roots and Heuristic Value of Linguistic Metaphors in Molecular Genetics. Part 2

2020 ◽  
Vol 63 (2) ◽  
pp. 46-62
Author(s):  
Suren T. Zolyan
Keyword(s):  
Information Processing ◽  
Genetic Information ◽  
Formal Organization ◽  
Dual Nature ◽  
Reading Frame ◽  
The Core ◽  
Genetic Information Processing ◽  
Cognitive Frame ◽  
Effective Instrument

We discuss the role of linguistic metaphors as a cognitive frame for the understanding of genetic information processing. The essential similarity between language and genetic information processing has been recognized since the very beginning, and many prominent scholars have noted the possibility of considering genes and genomes as texts or languages. Most of the core terms in molecular biology are based on linguistic metaphors. The processing of genetic information is understood as some operations on text – writing, reading and editing and their specification (encoding/decoding, proofreading, transcription, translation, reading frame). The concept of gene reading can be traced from the archaic idea of the equation of Life and Nature with the Book. Thus, the genetics itself can be metaphorically represented as some operations on text (deciphering, understanding, code-breaking, transcribing, editing, etc.), which are performed by scientists. At the same time linguistic metaphors portrayed gene entities also as having the ability of reading. In the case of such “bio-reading” some essential features similar to the processes of human reading can be revealed: this is an ability to identify the biochemical sequences based on their function in an abstract system and distinguish between type and its contextual tokens of the same type. Metaphors seem to be an effective instrument for representation, as they make possible a two-dimensional description: biochemical by its experimental empirical results and textual based on the cognitive models of comprehension. In addition to their heuristic value, linguistic metaphors are based on the essential characteristics of genetic information derived from its dual nature: biochemical by its substance, textual (or quasi-textual) by its formal organization. It can be concluded that linguistic metaphors denoting biochemical objects and processes seem to be a method of description and explanation of these heterogeneous properties.

Improving the questions we ask, with Psychology and Cognitive Conflict.

2018 ◽  
Author(s):  
Brett Buttliere
Keyword(s):  
Problem Solving ◽  
Scientific Method ◽  
Meaning Making ◽  
Cognitive Conflict ◽  
Empirical Literature ◽  
Present Evidence ◽  
Scientific Papers ◽  
Science In Society

Over the last decade, there have been many suggestions to improve how scientists answer their questions, but far fewer attempt to improve the questions scientists are asking in the first place. The goal of the paper is then to examine and summarize synthesize the evidence on how to ask the best questions possible. First is a brief review of the philosophical and empirical literature on how the best science is done, which implicitly but not explicitly mentions the role of psychology and especially cognitive conflict. Then we more closely focus on the psychology of the scientist, finding that they are humans, engaged in a meaning making process, and that cognitive conflict is a necessary input for any learning or change in the system. The scientific method is, of course, a specialized meaning making process. We present evidence for this central role of cognitive conflict in science by examining the most discussed scientific papers between 2013 and 2017, which are, in general, controversial and about big problems (e.g., whether vaccines cause autism, how often doctors kill us with their mistakes). Toward the end we discuss the role of science in society, suggesting science itself is an uncertainty reducing and problem solving enterprise. From this basis we encourage scientists to take riskier stances on bigger topics, for the good of themselves and society generally.

Exploring the Mechanism of Lingzhu San in Treating Febrile Seizures by Using Network Pharmacology

2020 ◽  
Vol 23 ◽  
Author(s):  
Xiao Zhou ◽  
Xiao-Fei Zhang ◽  
Dong-Yan Guo ◽  
Yan-Jun Yang ◽  
Lin Liu ◽  
...  
Keyword(s):  
Febrile Seizures ◽  
Network Pharmacology ◽  
Biological Processes ◽  
Active Compounds ◽  
Potential Core ◽  
R Language ◽  
The Core ◽  
Multiple Factors ◽  
Therapeutic Mechanism

Objective: Lingzhu San (LZS) is a traditional Chinese medicine (TCM) prescription which can be effective in treating febrile seizures (FS) and has few researches on the mechanisms. In order to better guide the clinical use of LZS, we used the research ideas and methods of network pharmacology to find the potential core compounds, targets and pathways of LZS in the complex TCM system for the treatment of FS, and predict the mechanism. Materials and Methods: Databases such as BATMAN, TCMSP, TCMID, and SWISS TARGET are used to mine the active compounds and targets of LZS, and the target information of FS was obtained through GENECARDS and OMIM. Using Venny2.1.0 and Cytoscape software to locked the potential core compounds and targets of FS. The R language and ClusterProfiler software package were adopt to enrich and analyze the KEGG and GO pathways of the core targets and the biological processes and potential mechanisms of the core targets were revealed. Results: 187 active compounds and 2113 target proteins of LZS were collected. And 38 potential core compounds, 35 core targets and 775 metabolic and functional pathways were screened which involved in mediating FS. Finally, the role of the core compounds, targets and pivotal pathways of LZS regulated FS in the pathogenesis and therapeutic mechanism of FS was discussed and clarified. Conclusions: In this paper, the multi-compounds, multi-targets and multi-pathways mechanism of LZS in the treatment of FS was preliminarily revealed through the analysis of network pharmacology data, which is consistent with the principle of multi-compounds compatibility of TCM prescriptions and unified treatment of diseases from multiple angles, and it provides a new way for TCM to treat complex diseases caused by multiple factors.

Acid ceramidase, a double-edged sword in cancer aggression: A minireview

2020 ◽  
Vol 20 ◽  
Author(s):  
Helen Shiphrah Vethakanraj ◽  
Niveditha Chandrasekaran ◽  
Ashok Kumar Sekar
Keyword(s):  
Cell Fate ◽  
Cancer Progression ◽  
Potential Role ◽  
Tumour Progression ◽  
Acid Ceramidase ◽  
The Core ◽  
The Past ◽  
Sphingosine 1 Phosphate ◽  
Key Enzyme

: Acid ceramidase (AC), the key enzyme of the ceramide metabolic pathway hydrolyzes pro-apoptotic ceramide to sphingosine, which by the action of sphingosine-1-kinase is metabolized to mitogenic sphingosine-1-phosphate. The intracellular level of AC determines ceramide/sphingosine-1-phosphate rheostat which in turn decides the cell fate. The upregulated AC expression during cancerous condition acts as a “double-edged sword” by converting pro-apoptotic ceramide to anti-apoptotic sphingosine-1-phosphate, wherein on one end, the level of ceramide is decreased and on the other end, the level of sphingosine-1-phosphate is increased, thus altogether aggravating the cancer progression. In addition, cancer cells with upregulated AC expression exhibited increased cell proliferation, metastasis, chemoresistance, radioresistance and numerous strategies were developed in the past to effectively target the enzyme. Gene silencing and pharmacological inhibition of AC sensitized the resistant cells to chemo/radiotherapy thereby promoting cell death. The core objective of this review is to explore AC mediated tumour progression and the potential role of AC inhibitors in various cancer cell lines/models.

The Fox Diet

2018 ◽  
Author(s):  
Yochai Benkler ◽  
Robert Faris ◽  
Hal Roberts
Keyword(s):  
First Year ◽  
Right Wing ◽  
Justice Department ◽  
Fox News ◽  
The Core ◽  
Deep State ◽  
Media Ecosystem ◽  
Conservative Media ◽  
The Right

This chapter focuses on the role of the dominant player in conservative media, Fox News, during the first year of Donald Trump’s presidency. It looks at three case studies to illustrate how Fox News used its position at the core of the right-wing media ecosystem repeatedly to mount propaganda attacks in support of Trump: the Michael Flynn firing in March 2017, when Fox adopted the “deep state” framing of the entire controversy; the James Comey firing and Robert Mueller appointment in May 2017; when Fox propagated the Seth Rich murder conspiracy; and in October and November, when the arrests of Paul Manafort and guilty plea of Flynn seemed to mark a new level of threat to the president, Fox reframed the Uranium One story as an attack on the integrity of the FBI and Justice Department officials in charge of the investigation.

scholarly journals The role of AGN activity in the building up of the BCG at z ∼ 1.6

2019 ◽  
Vol 15 (S356) ◽  
pp. 280-284
Author(s):  
Angela Bongiorno ◽  
Andrea Travascio
Keyword(s):  
Galaxy Cluster ◽  
Cluster Galaxy ◽  
X Ray ◽  
Groups Of Galaxies ◽  
Star Forming ◽  
The Core ◽  
The Galaxy ◽  
Multi Wavelength

AbstractXDCPJ0044.0-2033 is one of the most massive galaxy cluster at z ∼1.6, for which a wealth of multi-wavelength photometric and spectroscopic data have been collected during the last years. I have reported on the properties of the galaxy members in the very central region (∼ 70kpc × 70kpc) of the cluster, derived through deep HST photometry, SINFONI and KMOS IFU spectroscopy, together with Chandra X-ray, ALMA and JVLA radio data.In the core of the cluster, we have identified two groups of galaxies (Complex A and Complex B), seven of them confirmed to be cluster members, with signatures of ongoing merging. These galaxies show perturbed morphologies and, three of them show signs of AGN activity. In particular, two of them, located at the center of each complex, have been found to host luminous, obscured and highly accreting AGN (λ = 0.4−0.6) exhibiting broad Hα line. Moreover, a third optically obscured type-2 AGN, has been discovered through BPT diagram in Complex A. The AGN at the center of Complex B is detected in X-ray while the other two, and their companions, are spatially related to radio emission. The three AGN provide one of the closest AGN triple at z > 1 revealed so far with a minimum (maximum) projected distance of 10 kpc (40 kpc). The discovery of multiple AGN activity in a highly star-forming region associated to the crowded core of a galaxy cluster at z ∼ 1.6, suggests that these processes have a key role in shaping the nascent Brightest Cluster Galaxy, observed at the center of local clusters. According to our data, all galaxies in the core of XDCPJ0044.0-2033 could form a BCG of M* ∼ 1012Mȯ hosting a BH of 2 × 108−109Mȯ, in a time scale of the order of 2.5 Gyrs.

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