On the impact of soft hand-off in cellular systems

Author(s):  
Nidhi Hegde ◽  
Khosrow Sohraby
Keyword(s):  
Hand Off ◽  
2000 ◽  
Vol 28 (1) ◽  
pp. 178-187
Author(s):  
Nidhi Hegde ◽  
Khosrow Sohraby
Keyword(s):  
Hand Off ◽  

2021 ◽  
Author(s):  
Anuj K Yadav ◽  
Michael C. Lee ◽  
Melissa Lucero ◽  
Christopher J. Reinhardt ◽  
ShengZhang Su ◽  
...  

<p>Nitric oxide (NO) plays a critical role in acute and chronic inflammation. NO’s contributions to cancer are of particular interest due to its context-dependent bioactivities. For example, immune cells initially produce cytotoxic quantities of NO in response to the nascent tumor. However, it is believed that this fades over time and reaches a concentration that supports the tumor microenvironment (TME). These complex dynamics are further complicated by other factors, such as diet and oxygenation, making it challenging to establish a complete picture of NO’s impact on tumor progression. Although many activity-based sensing (ABS) probes for NO have been developed, only a small fraction have been employed <i>in vivo </i>and fewer yet are practical in cancer models where the NO concentration is < 200 nM. To overcome this outstanding challenge, we have developed BL<sub>660</sub>-NO, the first ABS probe for NIR bioluminescence imaging of NO in cancer. Owing to the low intrinsic background, high sensitivity, and deep tissue imaging capabilities of our design, BL<sub>660</sub>-NO was successfully employed to visualize endogenous NO in cellular systems, a human liver metastasis model, and a murine breast cancer model. Importantly, its exceptional performance facilitated the design of a dietary study to examine the impact of NO on the TME by varying the intake of fat. BL<sub>660</sub>-NO provides the first direct molecular evidence that intratumoral NO becomes elevated in mice fed a high-fat diet who became obese with larger tumors compared to control animals on a low-fat diet. These results indicate that an inflammatory diet can increase NO production via recruitment of macrophages and overexpression of iNOS which in turn can drive tumor progression.<br></p>


Author(s):  
Y. A. Bahei-El-Din ◽  
M. A. Zikry ◽  
A. Rajendran

The deformation fields and kinematics of woven composite material systems due to impact loads are analyzed and characterized for various structural parameters. Target plates comprised of woven composites with 3D preforms are considered. The analysis examines fully consolidated as well as cellular systems and simulates actual experiments. Solution of the nonlinear dynamic/contact problem was obtained by a meso-mechanics based finite element model. The results quantify experimental observations, which reveal distinct behavior under impact among nonporous and porous systems. It was found that wave propagation effects at incident energies in the order of 500 J are significant and lead to penetration at the impact face. Localized shear damage in the 3D woven system precede penetration in both the nonporous and the porous systems. The porous system is capable of dissipating more energy prior to penetration due to containment of local damage, which emanates from the void boundaries, within subsurface locations.


PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0257495
Author(s):  
Janine Riegert ◽  
Alexander Töpel ◽  
Jana Schieren ◽  
Renee Coryn ◽  
Stella Dibenedetto ◽  
...  

Biomaterial-driven modulation of cell adhesion and migration is a challenging aspect of tissue engineering. Here, we investigated the impact of surface-bound microgel arrays with variable geometry and adjustable cross-linking properties on cell adhesion and migration. We show that cell migration is inversely correlated with microgel array spacing, whereas directionality increases as array spacing increases. Focal adhesion dynamics is also modulated by microgel topography resulting in less dynamic focal adhesions on surface-bound microgels. Microgels also modulate the motility and adhesion of Sertoli cells used as a model for cell migration and adhesion. Both focal adhesion dynamics and speed are reduced on microgels. Interestingly, Gas2L1, a component of the cytoskeleton that mediates the interaction between microtubules and microfilaments, is dispensable for the regulation of cell adhesion and migration on microgels. Finally, increasing microgel cross-linking causes a clear reduction of focal adhesion turnover in Sertoli cells. These findings not only show that spacing and rigidity of surface-grafted microgels arrays can be effectively used to modulate cell adhesion and motility of diverse cellular systems, but they also form the basis for future developments in the fields of medicine and tissue engineering.


2021 ◽  
Author(s):  
Sagnik Sen ◽  
Ashmita Dey ◽  
Dwipanjan Sanyal ◽  
Ujjwal Maulik ◽  
Krishnananda Chattopadhyay

For neurodegenerative diseases, the impact of immunological markers is one of the modern research areas. It has been observed that neuroinflammation increases the cellular precipitation of some of the key proteins associated with neurodegenerative diseases. Therefore, the possibility of functional loss can be enhanced due to neuroinflammation which leads to the initiation of any related diseases. In this regard, autoantibodies, which are known for their autophagy nature, can be considered as key elements for early diagnostic as well as early therapeutics. In this article, we have proposed a comprehensive framework to unveil the diagnostic as well as the therapeutic possibility of the autoantibodies which are largely associated with Mild-Moderate Alzheimer's Disease, Early-Stage Parkinson's Disease, and Multiple Sclerosis. Here, we have introduced a new concept of average p-value where multiple p-values of an autoantibody in a singular disease have been considered as a multi-occurrence of that sample in cellular systems. Also, multiple proteins from a single protein family under a differentially expressed range have been prioritized. As a result, the top ten autoantibodies have been selected for further study and also considered as diagnostic markers. Interestingly, most of the selected autoantibodies are either cytokines or immunoglobulins. Subsequently, we have performed an evolutionary sequence-structure space study to identify the druggable structural facet for the selected autoantibodies. To make the therapeutic perspective more robust, we have introduced the concept of protein moonlighting. Hence, it provides more robustness in therapeutic identification. Finally, two autoantibodies i.e., Q9NYV4 and P01602 are identified as a novel marker.


2018 ◽  
Author(s):  
Sonja Zayni ◽  
Samar Damiati ◽  
Susana Moreno-Flores ◽  
Fabian Amman ◽  
Ivo Hofacker ◽  
...  

AbstractThe investigation of membrane proteins, key constituents of cells, is hampered by the difficulty and complexity of their in vitro synthesis, of unpredictable yield. Cell-free synthesis is herein employed to unravel the impact of the expression construct on gene transcription and translation, without the complex regulatory mechanisms of cellular systems. Through the systematic design of plasmids in the immediacy of the start of the target gene, it was possible to identify translation initiation and the conformation of mRNA as the main factors governing the cell-free expression efficiency of the human voltage dependent anion channel (VDAC), a relevant membrane protein in drug-based therapy. A simple translation initiation model was developed to quantitatively assess the expression potential for the designed constructs. A scoring function is proposed that quantifies the feasibility of formation of the translation initiation complex through the ribosome-mRNA hybridization energy and the accessibility of the mRNA segment binding to the ribosome. The scoring function enables to optimize plasmid sequences and semi-quantitatively predict protein expression efficiencies.


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