Integration of Biochemical and Mechanical Signals at the Nuclear Periphery: Impacts on Skin Development and Disease

Author(s):  
Rachel M. Stewart ◽  
Megan C. King ◽  
Valerie Horsley
2020 ◽  
Author(s):  
Ruhul Amin ◽  
Anjali Shukla ◽  
Jacqueline Jufen Zhu ◽  
Sohyoung Kim ◽  
Ping Wang ◽  
...  

Mechanical signals from the extracellular microenvironment have been implicated in tumor and metastatic progression. It remains unclear how these mechanical signals are transmitted to the cell nucleus to regulate gene expression in metastasis. In an attempt to characterize metastasis-associated polymorphisms in the non-coding regulatory regions of the genome, we identified nucleoporin NUP210 as a metastasis susceptibility gene for human estrogen receptor positive (ER+) breast cancer and a cellular mechanosensor. Polymorphisms in the mouse Nup210 promoter affect Nup210 transcription via alteration of CTCF binding. Depletion of Nup210 reduces lung metastasis in mouse models of breast cancer. Mechanistically, NUP210 interacts with histone H3.1/H3.2 at the nuclear periphery and prevents its heterochromatin (H3K27me3) modification to regulate mechanosensitive, metastasis- promoting gene expression. Upon Nup210 knockout, these mechanosensitive genes are differentially repositioned and become repressed due to heterochromatinization. As a result, Nup210 depletion decreases mechanotransduction and focal adhesion in vitro and circulating tumor cells in vivo. Our study provides a new insight into the role of nuclear pore protein in cellular mechanosensation and metastasis.


2020 ◽  
pp. 15-23
Author(s):  
V. M. Grechishnikov ◽  
E. G. Komarov

The design and operation principle of a multi-sensor Converter of binary mechanical signals into electrical signals based on a partitioned fiber-optic digital-to-analog Converter with a parallel structure is considered. The digital-to-analog Converter is made from a set of simple and technological (three to five digit) fiber-optic digital-to-analog sections. The advantages of the optical scheme of the proposed. Converter in terms of metrological and energy characteristics in comparison with single multi-bit converters are justified. It is shown that by increasing the number of digital-analog sections, it is possible to repeatedly increase the information capacity of a multi-sensor Converter without tightening the requirements for its manufacturing technology and element base. A mathematical model of the proposed Converter is developed that reflects the features of its operation in the mode of sequential time conversion of the input code vectors of individual fiber-optic sections into electrical analogues and the formation of the resulting output code vector.


Author(s):  
Hydar Muhsin Khalfa ◽  
Adnan Albideri ◽  
Haider Salih Jaffat

The integumentary system covers the surface of the embryo (skin) and its specialized skin structures including hair, nails, sweat glands, mammary glands and teeth. During fetal skin development, the epidermis changes from a single layer of ectodermal cells at 7–8 days of gestation into a more apparent stratified, keratinized epithelium at 22–24 weeks. The aim of the study is to identify the histological and cytological changes that take place during neonatal and adult epidermis development. Human neonatal and adult samples were obtained from fully informed, consenting parent or releatives from Al-hilla mortary / Iraq. Neonatal samples were obtained from neonates after sudden deaths from maternity wards. Anatomical Sites included abdomen, forehead, back, shoulder and feet sole. A totoal of 15 neonates and 10 mature adults were used for this study. Fresh tissues were sectioned using a freezing cryostat. Tissues were sectioned at 5µm in -24°C and collected on microscopic slides. Slides were allowed to air dry for 30 min prior to hematoxyline and eosin staining. Tissues were also photographed using scanning electron microscopy SEM. Cytological measurements were taken using image j software and data was analysed using graph prism. Various cytological and histological changes takes place during neonatal and adult and epidermis development. Our study shows the stages of fair follicule formation as well as number of nucleated layers present at each stage of development and at different anatomical sites. Major histological changes takes places during the transition frm a neonate to a mature adult including the number of basal cells and epidermal thickness depending on the anatomical site.


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