scholarly journals The conserved single-cleavage mechanism of animal DROSHA enzymes

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Thuy Linh Nguyen ◽  
Trung Duc Nguyen ◽  
Tuan Anh Nguyen
Keyword(s):  
The Other ◽  
Cellular Functions ◽  
Rnase Iii ◽  
Internal Loop ◽  
Cleavage Activity ◽  
Dsrna Binding ◽  
Human Rnase ◽  
The One ◽  
Enzymatic Mechanisms ◽  
Lower Stem

AbstractRNase III enzymes typically cleave both strands of double-stranded RNAs (dsRNAs). We recently discovered that a human RNase III, DROSHA, exhibits a single cleavage on the one strand of primary microRNAs (pri-miRNAs). This study revealed that DROSHAs from the other animals, including worms and flies, also show the single cleavage on dsRNAs. Furthermore, we demonstrated that the mechanism of single cleavage is conserved in animal DROSHA enzymes. In addition, the dsRNA-binding domain (dsRBD) and a 3p-strand cleavage-supporting helix (3pCSH) of the DROSHA enzymes foster a weak single cleavage on one strand, which ensures their double cleavages. Disrupting the interaction of dsRBD-RNA and 3pCSH-RNA by an internal loop (IL) and a 3pCSH-loop in the lower stem of pri-miRNAs, respectively, inhibits one of the double cleavages of DROSHAs, and this results in the single cleavage. Our findings expand our understanding of the enzymatic mechanisms of animal DROSHAs. They also indicate that there are currently unknown cellular functions of DROSHA enzymes using their single cleavage activity.

scholarly journals The internal loops in the lower stem of primary microRNA transcripts facilitate single cleavage of human Microprocessor

2020 ◽  
Vol 48 (5) ◽  
pp. 2579-2593 ◽  
Author(s):  
Thuy Linh Nguyen ◽  
Trung Duc Nguyen ◽  
Sheng Bao ◽  
Shaohua Li ◽  
Tuan Anh Nguyen
Keyword(s):  
Mirna Expression ◽  
Human Cells ◽  
Rnase Iii ◽  
Mirna Processing ◽  
Internal Loop ◽  
Alternative Approach ◽  
Microprocessor Complex ◽  
Internal Loops ◽  
Lower Stem

Abstract The human Microprocessor complex cleaves primary microRNA (miRNA) transcripts (pri-miRNAs) to initiate miRNA synthesis. Microprocessor consists of DROSHA (an RNase III enzyme), and DGCR8. DROSHA contains two RNase III domains, RIIIDa and RIIIDb, which simultaneously cleave the 3p- and 5p-strands of pri-miRNAs, respectively. In this study, we show that the internal loop located in the lower stem of numerous pri-miRNAs selectively inhibits the cleavage of Microprocessor on their 3p-strand, thereby, facilitating the single cleavage on their 5p-strand. This single cleavage does not lead to the production of miRNA but instead, it downregulates miRNA expression. We also demonstrate that by manipulating the size of the internal loop in the lower stem of pri-miRNAs, we can alter the ratio of single-cut to double-cut products resulted from the catalysis of Microprocessor, thus changing miRNA production in the in vitro pri-miRNA processing assays and in human cells. Therefore, the oscillating level of the single cleavage suggests another way of regulation of miRNA expression and offers an alternative approach to miRNA knockdown.

scholarly journals A Symphony of Regulations Centered onp63to Control Development of Ectoderm-Derived Structures

2011 ◽  
Vol 2011 ◽  
pp. 1-13 ◽  
Author(s):  
Luisa Guerrini ◽  
Antonio Costanzo ◽  
Giorgio R. Merlo
Keyword(s):  
Current Knowledge ◽  
The Other ◽  
Preclinical Studies ◽  
Cellular Functions ◽  
Cellular Models ◽  
Molecular Approaches ◽  
Related Transcription Factor ◽  
The One ◽  
Potential Exploitation

The p53-related transcription factor p63 is critically important for basic cellular functions during development of the ectoderm and derived structure and tissues, including skin, limb, palate, and hair. On the one side, p63 is required to sustain the proliferation of keratinocyte progenitors, while on the other side it is required for cell stratification, commitment to differentiate, cell adhesion, and epithelial-mesenchymal signaling. Molecules that are components or regulators of the p63 pathway(s) are rapidly being identified, and it comes with no surprise that alterations in the p63 pathway lead to congenital conditions in which the skin and other ectoderm-derived structures are affected. In this paper, we summarize the current knowledge of the molecular and cellular regulations centered on p63, derived from the comprehension of p63-linked human diseases and the corresponding animal models, as well as from cellular models and high-throughput molecular approaches. We point out common themes and features, that allow to speculate on the possible role of p63 downstream events and their potential exploitation in future attempts to correct the congenital defect in preclinical studies.

Note on Selection of Coordinate Systems for Geodynamics

1975 ◽  
Vol 26 ◽  
pp. 395-407
Author(s):  
S. Henriksen
Keyword(s):  
Sea Level ◽  
The Other ◽  
Coordinate Systems ◽  
Mean Sea Level ◽  
The Earth ◽  
The One ◽  
Static Systems ◽  
Selection Of

The first question to be answered, in seeking coordinate systems for geodynamics, is: what is geodynamics? The answer is, of course, that geodynamics is that part of geophysics which is concerned with movements of the Earth, as opposed to geostatics which is the physics of the stationary Earth. But as far as we know, there is no stationary Earth – epur sic monere. So geodynamics is actually coextensive with geophysics, and coordinate systems suitable for the one should be suitable for the other. At the present time, there are not many coordinate systems, if any, that can be identified with a static Earth. Certainly the only coordinate of aeronomic (atmospheric) interest is the height, and this is usually either as geodynamic height or as pressure. In oceanology, the most important coordinate is depth, and this, like heights in the atmosphere, is expressed as metric depth from mean sea level, as geodynamic depth, or as pressure. Only for the earth do we find “static” systems in use, ana even here there is real question as to whether the systems are dynamic or static. So it would seem that our answer to the question, of what kind, of coordinate systems are we seeking, must be that we are looking for the same systems as are used in geophysics, and these systems are dynamic in nature already – that is, their definition involvestime.

Stories and the Self

2020 ◽  
Vol 32 (2) ◽  
pp. 47-58 ◽  
Author(s):  
Stefan Krause ◽  
Markus Appel
Keyword(s):  
Meta Analysis ◽  
The Self ◽  
The Other ◽  
Lower Degree ◽  
Contrast Effects ◽  
Self Perception ◽  
Self Perceptions ◽  
Other Hand ◽  
The One ◽  
Implicit And Explicit

Abstract. Two experiments examined the influence of stories on recipients’ self-perceptions. Extending prior theory and research, our focus was on assimilation effects (i.e., changes in self-perception in line with a protagonist’s traits) as well as on contrast effects (i.e., changes in self-perception in contrast to a protagonist’s traits). In Experiment 1 ( N = 113), implicit and explicit conscientiousness were assessed after participants read a story about either a diligent or a negligent student. Moderation analyses showed that highly transported participants and participants with lower counterarguing scores assimilate the depicted traits of a story protagonist, as indicated by explicit, self-reported conscientiousness ratings. Participants, who were more critical toward a story (i.e., higher counterarguing) and with a lower degree of transportation, showed contrast effects. In Experiment 2 ( N = 103), we manipulated transportation and counterarguing, but we could not identify an effect on participants’ self-ascribed level of conscientiousness. A mini meta-analysis across both experiments revealed significant positive overall associations between transportation and counterarguing on the one hand and story-consistent self-reported conscientiousness on the other hand.

Radioimmunotherapy for treatment of acute myeloid leukaemia and myelodysplastic syndrome

2005 ◽  
Vol 44 (03) ◽  
pp. 107-117
Author(s):  
R. G. Meyer ◽  
W. Herr ◽  
A. Helisch ◽  
P. Bartenstein ◽  
I. Buchmann
Keyword(s):  
Acute Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Primary Tumour ◽  
The Other ◽  
Haematopoietic Stem Cell ◽  
Other Hand ◽  
Primary Reduction ◽  
The One ◽  
Acute Myeloid

SummaryThe prognosis of patients with acute myeloid leukaemia (AML) has improved considerably by introduction of aggressive consolidation chemotherapy and haematopoietic stem cell transplantation (SCT). Nevertheless, only 20-30% of patients with AML achieve long-term diseasefree survival after SCT. The most common cause of treatment failure is relapse. Additionally, mortality rates are significantly increased by therapy-related causes such as toxicity of chemotherapy and complications of SCT. Including radioimmunotherapies in the treatment of AML and myelodyplastic syndrome (MDS) allows for the achievement of a pronounced antileukaemic effect for the reduction of relapse rates on the one hand. On the other hand, no increase of acute toxicity and later complications should be induced. These effects are important for the primary reduction of tumour cells as well as for the myeloablative conditioning before SCT.This paper provides a systematic and critical review of the currently used radionuclides and immunoconjugates for the treatment of AML and MDS and summarizes the literature on primary tumour cell reductive radioimmunotherapies on the one hand and conditioning radioimmunotherapies before SCT on the other hand.

Das Ende der Postdemokratie, den Pessimismus überwinden.

2017 ◽  
Vol 47 (188) ◽  
pp. 487-494
Author(s):  
Daniel Mullis
Keyword(s):  
Political Thought ◽  
Social Dynamics ◽  
Social Conditions ◽  
The Other ◽  
Economic Decline ◽  
Far Right ◽  
Windows Of Opportunity ◽  
Political Events ◽  
Political Struggles ◽  
The One

In recent years, political and social conditions have changed dramatically. Many analyses help to capture these dynamics. However, they produce political pessimism: on the one hand there is the image of regression and on the other, a direct link is made between socio-economic decline and the rise of the far-right. To counter these aspects, this article argues that current political events are to be understood less as ‘regression’ but rather as a moment of movement and the return of deep political struggles. Referring to Jacques Ranciere’s political thought, the current conditions can be captured as the ‘end of post-democracy’. This approach changes the perspective on current social dynamics in a productive way. It allows for an emphasis on movement and the recognition of the windows of opportunity for emancipatory struggles.

Tolerance is theoretical and practical principles

1996 ◽  
pp. 13-23
Author(s):  
Mykhailo Babiy
Keyword(s):  
Religious Diversity ◽  
The Other ◽  
Nodal Points ◽  
Characteristic Features ◽  
The One ◽  
Ukrainian Society

Political ideological pluralism, religious diversity are characteristic features of modern Ukrainian society. On the one hand, multiculturalism, socio-political, religious differentiation of the latter appear as important characteristics of its democracy, as a practical expression of freedom, on the other - as a factor that led to the deconsocialization of society, gave rise to "nodal points" of tension, confrontational processes, in particular, in political and religious spheres.

The Salvage of Ideas: Schumpeter and the Core Problems Still Confronting Economics

2003 ◽  
pp. 15-26
Author(s):  
P. Wynarczyk
Keyword(s):  
The Other ◽  
The Core ◽  
Other Hand ◽  
The One

Two aspects of Schumpeter' legacy are analyzed in the article. On the one hand, he can be viewed as the custodian of the neoclassical harvest supplementing to its stock of inherited knowledge. On the other hand, the innovative character of his works is emphasized that allows to consider him a proponent of hetherodoxy. It is stressed that Schumpeter's revolutionary challenge can lead to radical changes in modern economics.

Hidden “holes” in the capital of banks and the supply of credit to the real sector of economy

2018 ◽  
pp. 49-68 ◽  
Author(s):  
M. E. Mamonov
Keyword(s):  
Credit Risk ◽  
The Other ◽  
Real Sector ◽  
Capital Management ◽  
Loan Loss ◽  
Short Term ◽  
The Real ◽  
Ex Post ◽  
The One

Our analysis documents that the existence of hidden “holes” in the capital of not yet failed banks - while creating intertemporal pressure on the actual level of capital - leads to changing of maturity of loans supplied rather than to contracting of their volume. Long-term loans decrease, whereas short-term loans rise - and, what is most remarkably, by approximately the same amounts. Standardly, the higher the maturity of loans the higher the credit risk and, thus, the more loan loss reserves (LLP) banks are forced to create, increasing the pressure on capital. Banks that already hide “holes” in the capital, but have not yet faced with license withdrawal, must possess strong incentives to shorten the maturity of supplied loans. On the one hand, it raises the turnovers of LLP and facilitates the flexibility of capital management; on the other hand, it allows increasing the speed of shifting of attracted deposits to loans to related parties in domestic or foreign jurisdictions. This enlarges the potential size of ex post revealed “hole” in the capital and, therefore, allows us to assume that not every loan might be viewed as a good for the economy: excessive short-term and insufficient long-term loans can produce the source for future losses.

Global Economic Crisis of 2008-2009: Sources and Roots

2009 ◽  
pp. 18-31
Author(s):  
G. Rapoport ◽  
A. Guerts
Keyword(s):  
Oil And Gas ◽  
Trade Deficit ◽  
Developed Countries ◽  
The Other ◽  
Energy Resources ◽  
Market Mechanisms ◽  
Production Output ◽  
The One ◽  
To Receive ◽  
Partial Destruction

In the article the global crisis of 2008-2009 is considered as superposition of a few regional crises that occurred simultaneously but for different reasons. However, they have something in common: developed countries tend to maintain a strong level of social security without increasing the real production output. On the one hand, this policy has resulted in trade deficit and partial destruction of market mechanisms. On the other hand, it has clashed with the desire of several oil and gas exporting countries to receive an exclusive price for their energy resources.

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