Exploring the effects of a dysfunctional nuclear matrix

2008 ◽  
Vol 36 (6) ◽  
pp. 1378-1383 ◽  
Author(s):  
Lauren S. Elcock ◽  
Joanna M. Bridger
Keyword(s):  
Dna Repair ◽  
Nuclear Envelope ◽  
Nuclear Structure ◽  
Nuclear Matrix ◽  
Functional Significance ◽  
Scientific Community ◽  
Envelope Proteins ◽  
General Acceptance ◽  
The Impact ◽  
Nuclear Processes

The nuclear matrix has remained a contentious structure for decades; many believe that it is an artefact of harsh non-physiological procedures. However, its visualization using milder experimental techniques is leading to its general acceptance by the scientific community. It is a permanent network of core filaments underlying thicker fibres which is proposed to be a platform for numerous important nuclear activities such as transcription and DNA repair. Interestingly, A- and B-type lamin proteins and emerin are components of this nuclear structure; however, they are often referred to only as nuclear envelope proteins. The present mini-review intends to provide an overview of the nuclear matrix, mentioning both its constituents and functional significance. The impact of disease-causing mutations in both emerin and lamin proteins on the structure's ability to regulate and mediate nuclear processes is then discussed.

scholarly journals DNA damage in 3D constricted migration or after lamin-A depletion in 2D: shared mechanisms of repair factor mis-localization under nuclear stress

2016 ◽  
Author(s):  
Yuntao Xia ◽  
Jerome Irianto ◽  
Charlotte R. Pfeifer ◽  
Jiazheng Ji ◽  
Irena L. Ivanovska ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Nuclear Envelope ◽  
Nuclear Structure ◽  
Lamin A ◽  
Soft Matrix ◽  
Progeroid Syndromes ◽  
Standard Culture ◽  
Repair Factor ◽  
Insight Into

AbstractCells that migrate through small, rigid pores and that have normal levels of the nuclear structure protein lamin-A exhibit an increase in DNA damage, which is also observed with lamin-A depletion in diseases such as cancer and with many lamin-A mutations. Here we show nuclear envelope rupture is a shared feature that increases in standard culture after lamin-A knockdown, which causes nuclear loss of multiple DNA repair factors and increased DNA damage. Some repair factors are merely mis-localized to cytoplasm whereas others are partially depleted unless rescued by lamin-A expression. Compared to standard cultures on rigid glass coverslips, the growth of lamin-A low cells on soft matrix relaxes cytoskeletal stress on the nucleus, suppresses the mis-localization of DNA repair factors, and minimizes DNA damage nearly to wildtype levels. Conversely, constricted migration of the lamin-A low cells causes abnormally high levels of DNA damage, consistent with sustained loss of repair factors. The findings add insight into why monogenic progeroid syndromes that often associate with increased DNA damage and predominantly impact cells in stiff tissues result from mutations only in lamin-A or DNA repair factors.

The Role of HOP in Emerin-Mediated Nuclear Structure

2017 ◽  
Author(s):  
◽  
Sarah Naulikha Kituyi
Keyword(s):  
Nuclear Envelope ◽  
Nuclear Structure ◽  
Cell Biology ◽  
Cell Mass ◽  
Hek293t Cell ◽  
Hek293 Cells ◽  
Term Survival ◽  
Over Expression ◽  
The Impact

A vital component of the integral nuclear membrane is emerin, a Lamin Emerin and Man1 (LEM) domain protein whose concentration determines the levels of partner proteins that together constitute the structure of the nuclear envelope. Deficiencies in any of these proteins causes the failure of the structure and assembly and disassembly of the nuclear envelope, which disrupts chromosome segregation and nuclear compartmentalization that are both associated with disease. Emerin also localizes in the cytoplasm where it is implicated in the structure of the cytoskeleton via interaction with tubulin and actin and thus its deficiency may equally contribute to the collapse of the cytoskeleton. The Hsp70-Hsp90 organising protein (Hop) functions as a cochaperone for entry of client proteins into the Hsp90 folding cycle. Hop is upregulated in cancer and regulates a number of cell biology processes via interactions with proteins independently of Hsp90. In a previous study using global whole cell mass spectrometry, emerin was shown to be the most significantly down regulated protein in Hop depleted cell lysates. In this current study, it was postulated that emerin interacts with Hop, and this interaction regulates the stability, and level of emerin in the nucleus which impacts on the structure of the nuclear envelope. We used HEK293T cell lines stably expressing shRNA against Hop, emerin and a non-targeting control alongside the over expression of Hop in HEK293 cells to determine the effect of Hop levels on emerin expression and vice versa via Western blotting. The effect of Hop on the localization of emerin was assessed via subcellullar fractionation and confocal microscopy, while the impact on the structure of the nucleus was determined by transmission electron microscopy (TEM). We established that the depletion of Hop using shRNA and the over expression of Hop both result in the proteasomal and lysosomal degradation of emerin. Co-immunoprecipitation assays confirmed that Hop and emerin are in a common complex, which was not dependent on the presence of Hsp90. Loss of Hop or emerin led to a deformation of nuclear structure and a statistically significant decrease in nuclear size compared to control cells and was associated with an increase in the levels of nuclear protein, lamin A-C. Loss of emerin and Hop resulted in increased long term cell survival, but only after restriction of the nucleus when the cells had migrated across a transwell membrane. Taken together, the results obtained suggest that Hop acts as a scaffold for the stabilization of emerin and that the effects of Hop depletion on the structure of the nucleus and long term survival are mediated via the depletion of emerin.

On the general acceptance of confessions research: Opinions of the scientific community.

2018 ◽  
Vol 73 (1) ◽  
pp. 63-80 ◽  
Author(s):  
Saul M. Kassin ◽  
Allison D. Redlich ◽  
Fabiana Alceste ◽  
Timothy J. Luke
Keyword(s):  
Scientific Community ◽  
General Acceptance

ON THE CLASSIFICATION OF DIGITAL TECHNOLOGIES IN CIVIL PROCESS

2019 ◽  
pp. 27-35
Author(s):  
Alexandr Neznamov
Keyword(s):  
Information Processing ◽  
Scientific Community ◽  
Digital Technologies ◽  
Significant Feature ◽  
Legal Proceedings ◽  
Civil Process ◽  
Civil Proceedings ◽  
Processing Information ◽  
The Impact

Digital technologies are no longer the future but are the present of civil proceedings. That is why any research in this direction seems to be relevant. At the same time, some of the fundamental problems remain unattended by the scientific community. One of these problems is the problem of classification of digital technologies in civil proceedings. On the basis of instrumental and genetic approaches to the understanding of digital technologies, it is concluded that their most significant feature is the ability to mediate the interaction of participants in legal proceedings with information; their differentiating feature is the function performed by a particular technology in the interaction with information. On this basis, it is proposed to distinguish the following groups of digital technologies in civil proceedings: a) technologies of recording, storing and displaying (reproducing) information, b) technologies of transferring information, c) technologies of processing information. A brief description is given to each of the groups. Presented classification could serve as a basis for a more systematic discussion of the impact of digital technologies on the essence of civil proceedings. Particularly, it is pointed out that issues of recording, storing, reproducing and transferring information are traditionally more «technological» for civil process, while issues of information processing are more conceptual.

scholarly journals A Risk-Based Strategy for Evaluating Mitigation Options for Process-Formed Compounds in Food

2016 ◽  
Vol 35 (3) ◽  
pp. 358-370 ◽  
Author(s):  
Paul Hanlon ◽  
Gregory P. Brorby ◽  
Mansi Krishan
Keyword(s):  
North America ◽  
Decision Tree ◽  
Scientific Community ◽  
Life Sciences ◽  
Technical Committee ◽  
Global Approach ◽  
Chemical Safety ◽  
The Public ◽  
The North ◽  
The Impact

Processing (eg, cooking, grinding, drying) has changed the composition of food throughout the course of human history; however, awareness of process-formed compounds, and the potential need to mitigate exposure to those compounds, is a relatively recent phenomenon. In May 2015, the North American Branch of the International Life Sciences Institute (ILSI North America) Technical Committee on Food and Chemical Safety held a workshop on the risk-based process for mitigation of process-formed compounds. This workshop aimed to gain alignment from academia, government, and industry on a risk-based process for proactively assessing the need for and benefit of mitigation of process-formed compounds, including criteria to objectively assess the impact of mitigation as well as research needed to support this process. Workshop participants provided real-time feedback on a draft framework in the form of a decision tree developed by the ILSI North America Technical Committee on Food and Chemical Safety to a panel of experts, and they discussed the importance of communicating the value of such a process to the larger scientific community and, ultimately, the public. The outcome of the workshop was a decision tree that can be used by the scientific community and could form the basis of a global approach to assessing the risks associated with mitigation of process-formed compounds.

Considerations in the isolation of rat liver nuclear matrix, nuclear envelope, and pore complex lamina

1981 ◽  
Vol 132 (1) ◽  
pp. 105-123 ◽  
Author(s):  
Scott H. Kaufmann ◽  
Donald S. Coffey ◽  
Joel H. Shaper
Keyword(s):  
Nuclear Envelope ◽  
Rat Liver ◽  
Nuclear Matrix

scholarly journals Paraben Compounds—Part I: An Overview of Their Characteristics, Detection, and Impacts

2021 ◽  
Vol 11 (5) ◽  
pp. 2307
Author(s):  
João Lincho ◽  
Rui C. Martins ◽  
João Gomes
Keyword(s):  
Scientific Community ◽  
Wastewater Treatment Plants ◽  
Analytical Techniques ◽  
Water Sources ◽  
Human Tissues ◽  
Antimicrobial Compounds ◽  
Toxicological Studies ◽  
The Impact ◽  
Different Sources ◽  
Different Water Sources

Parabens are widely used in different industries as preservatives and antimicrobial compounds. The evolution of analytical techniques allowed the detection of these compounds in different sources at µg/L and ng/L. Until today, parabens were already found in water sources, air, soil and even in human tissues. The impact of parabens in humans, animals and in ecosystems are a matter of discussion within the scientific community, but it is proven that parabens can act as endocrine disruptors, and some reports suggest that they are carcinogenic compounds. The presence of parabens in ecosystems is mainly related to wastewater discharges. This work gives an overview about the paraben problem, starting with their characteristics and applications. Moreover, the dangers related to their usage were addressed through the evaluation of toxicological studies over different species as well as of humans. Considering this, paraben detection in different water sources, wastewater treatment plants, humans and animals was analyzed based on literature results. A review of European legislation regarding parabens was also performed, presenting some considerations for the use of parabens.

The Impact of Solar Winds on Navigation Aids

1999 ◽  
Vol 52 (1) ◽  
pp. 42-46 ◽  
Author(s):  
W. H. Sandford
Keyword(s):  
Solar Wind ◽  
Media Coverage ◽  
Scientific Community ◽  
The United States ◽  
Public Attention ◽  
Remote Imaging ◽  
Solar Winds ◽  
New Information ◽  
Recent Developments ◽  
The Impact

Recent developments in remote imaging equipment carried on satellites have given the scientific community a vast amount of new information about the Sun and its atmosphere. Media coverage of the remarkable discoveries accompanied by impressive images of the Sun's atmosphere, and linkage to the loss of a television satellite over the United States, have focused public attention on the existence and effects of the Solar Wind. This paper sets out to illustrate the impact of the Solar Wind on radio aids to navigation, and to look at the possible effects on present and proposed systems.

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