scholarly journals Directly observing intracellular nanoparticle formation with nanocomputed tomography

2020 ◽  
Vol 6 (43) ◽  
pp. eaba3190
Author(s):  
Miaomiao Zhang ◽  
Yong Guan ◽  
Zheng Dang ◽  
Pinggen Zhang ◽  
Zhen Zheng ◽  
...  
Keyword(s):  
Absorption Coefficient ◽  
Small Molecule ◽  
Hela Cells ◽  
Condensation Reaction ◽  
Linear Absorption Coefficient ◽  
Linear Absorption ◽  
X Ray ◽  
Nanoparticle Formation ◽  
Near Future

Directly observing intracellular nanostructure formation remains challenging. In this work, using a rationally designed small-molecule 4-nitrobenzyl carbamate–Cys(SEt)-Asp-Asp-Phe(iodine)–2-cyano-benzothiazole (NBC-Iod-CBT), we directly observed intracellular nanoparticle formation with nanocomputed tomography (nano-CT). In vitro, upon glutathione reduction and nitroreductase (NTR) cleavage, NBC-Iod-CBT undergoes a CBT-Cys click condensation reaction to self-assemble nanoparticles Iod-CBT-NPs with an average linear absorption coefficient (LAC) value of 0.182 ± 0.078 μm−1 to x-ray. Nano-CT imaging of the NBC-Iod-CBT–treated, NTR-overexpressing HeLa cells showed the existence of Iod-CBT-NPs in their cytoplasm with an average LAC value of 0.172 ± 0.032 μm−1. We anticipate that our strategy could help people to deeply understand the formation mechanism of intracellular nanostructures in the near future.

Experimental Implications of X-Ray Standing Waves

2014 ◽  
pp. 462-482
Keyword(s):  
Absorption Coefficient ◽  
Standing Waves ◽  
Anomalous Absorption ◽  
X Ray Diffraction ◽  
Linear Absorption Coefficient ◽  
Linear Absorption ◽  
X Ray ◽  
Basic Concepts

Basic concepts of dynamic X-ray diffraction are applied in distinguishing between the propagation along the atomic planes characterized by the linear absorption coefficient and the perpendicular propagation on the atomic planes. Propagation is responsible for the generation of the standing waves through the anomalous absorption coefficient on dispersion branches of diffraction.

An X-Ray Absorption Technique for Measurement of Coat Weight on Paper

1960 ◽  
Vol 4 ◽  
pp. 309-318
Author(s):  
Haydn H. Murray ◽  
William D. Johns
Keyword(s):  
Absorption Coefficient ◽  
Production Control ◽  
Absorption Method ◽  
Linear Absorption Coefficient ◽  
Linear Absorption ◽  
Absorbing Medium ◽  
X Ray ◽  
Coating Layers ◽  
X Ray Absorption ◽  
Absorption Technique

AbstractAn X-ray absorption method was utilized to determine rapidly and precisely the thickness and weight of inorganic coating layers applied to paper. The mass absorption coefficient μ/ρ was calculated for kaolins and substituted in the following formulawhere I is the X-ray intensity after passing through a medium whose thickness is x centimeters, I0 Is the X-ray intensity before passing through a medium, μ. is the linear absorption coefficient, and ρ is the density of the absorbing medium.The film thickness was calculated and related to coat weight. Coated sheets of variable basis weight, utilizing different adhesives and coat weights, were used. The method is rapid and coating thicknesses can be determined with an accuracy of plus or minus 0.5μ and coat weight of plus or minus 0.2 lb. It is believed that the method can be adapted for production control on the paper coating machines.

scholarly journals A small molecule compound with an indole moiety inhibits the main protease of SARS-CoV-2 and blocks virus replication

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Shin-ichiro Hattori ◽  
Nobuyo Higashi-Kuwata ◽  
Hironori Hayashi ◽  
Srinivasa Rao Allu ◽  
Jakka Raghavaiah ◽  
...  
Keyword(s):  
Small Molecule ◽  
Covalent Bond ◽  
Amino Acid Residues ◽  
X Ray ◽  
Viral Breakthrough ◽  
Main Protease ◽  
Small Molecule Compound ◽  
Polar Interactions ◽  
High Concentrations

AbstractExcept remdesivir, no specific antivirals for SARS-CoV-2 infection are currently available. Here, we characterize two small-molecule-compounds, named GRL-1720 and 5h, containing an indoline and indole moiety, respectively, which target the SARS-CoV-2 main protease (Mpro). We use VeroE6 cell-based assays with RNA-qPCR, cytopathic assays, and immunocytochemistry and show both compounds to block the infectivity of SARS-CoV-2 with EC50 values of 15 ± 4 and 4.2 ± 0.7 μM for GRL-1720 and 5h, respectively. Remdesivir permitted viral breakthrough at high concentrations; however, compound 5h completely blocks SARS-CoV-2 infection in vitro without viral breakthrough or detectable cytotoxicity. Combination of 5h and remdesivir exhibits synergism against SARS-CoV-2. Additional X-ray structural analysis show that 5h forms a covalent bond with Mpro and makes polar interactions with multiple active site amino acid residues. The present data suggest that 5h might serve as a lead Mpro inhibitor for the development of therapeutics for SARS-CoV-2 infection.

scholarly journals Promising Recent Strategies with Potential Clinical Translational Value to Combat Antibacterial Resistant Surge

Medicines ◽  
2019 ◽  
Vol 6 (1) ◽  
pp. 21 ◽  
Author(s):  
Partha Karmakar ◽  
Vishwanath Gaitonde
Keyword(s):  
Small Molecule ◽  
Multiple Drug Resistance ◽  
Resistance Mechanism ◽  
Multiple Drug ◽  
Antibacterial Efficacy ◽  
Small Particles ◽  
Near Future ◽  
Metal Polymer

Multiple drug resistance (MDR) for the treatment of bacterial infection has been a significant challenge since the beginning of the 21st century. Many of the small molecule-based antibiotic treatments have failed on numerous occasions due to a surge in MDR, which has claimed millions of lives worldwide. Small particles (SPs) consisting of metal, polymer or carbon nanoparticles (NPs) of different sizes, shapes and forms have shown considerable antibacterial effect over the past two decades. Unlike the classical small-molecule antibiotics, the small particles are less exposed so far to the bacteria to trigger a resistance mechanism, and hence have higher chances of fighting the challenge of the MDR process. Until recently, there has been limited progress of clinical treatments using NPs, despite ample reports of in vitro antibacterial efficacy. In this review, we discuss some recent and unconventional strategies that have explored the antibacterial efficacy of these small particles, alone and in combination with classical small molecules in vivo, and demonstrate possibilities that are favorable for clinical translations in near future.

scholarly journals Phase-contrast 3D tomography of HeLa cells grown in PLLA polymer electrospun scaffolds using synchrotron X-rays

2020 ◽  
Vol 27 (1) ◽  
pp. 158-163 ◽  
Author(s):  
A. Bhartiya ◽  
K. Madi ◽  
C. M. Disney ◽  
L. Courtois ◽  
A. Jupe ◽  
...  
Keyword(s):  
Cell Growth ◽  
Hela Cells ◽  
Phase Contrast ◽  
Fiber Diameter ◽  
Large Field ◽  
X Rays ◽  
Nondestructive Technique ◽  
X Ray ◽  
Electrospun Scaffolds

Advanced imaging is useful for understanding the three-dimensional (3D) growth of cells. X-ray tomography serves as a powerful noninvasive, nondestructive technique that can fulfill these purposes by providing information about cell growth within 3D platforms. There are a limited number of studies taking advantage of synchrotron X-rays, which provides a large field of view and suitable resolution to image cells within specific biomaterials. In this study, X-ray synchrotron radiation microtomography at Diamond Light Source and advanced image processing were used to investigate cellular infiltration of HeLa cells within poly L-lactide (PLLA) scaffolds. This study demonstrates that synchrotron X-rays using phase contrast is a useful method to understand the 3D growth of cells in PLLA electrospun scaffolds. Two different fiber diameter (2 and 4 µm) scaffolds with different pore sizes, grown over 2, 5 and 8 days in vitro, were examined for infiltration and cell connectivity. After performing visualization by segmentation of the cells from the fibers, the results clearly show deeper cell growth and higher cellular interconnectivity in the 4 µm fiber diameter scaffold. This indicates the potential for using such 3D technology to study cell–scaffold interactions for future medical use.

scholarly journals A small-molecule inhibitor of Haspin alters the kinetochore functions of Aurora B

2012 ◽  
Vol 199 (2) ◽  
pp. 269-284 ◽  
Author(s):  
Anna De Antoni ◽  
Stefano Maffini ◽  
Stefan Knapp ◽  
Andrea Musacchio ◽  
Stefano Santaguida
Keyword(s):  
Phosphatase Activity ◽  
Small Molecule ◽  
Hela Cells ◽  
Spindle Assembly Checkpoint ◽  
Histone H3 ◽  
Aurora B ◽  
Molecule Inhibitor ◽  
Chromosome Passenger Complex ◽  
Kinase A

By phosphorylating Thr3 of histone H3, Haspin promotes centromeric recruitment of the chromosome passenger complex (CPC) during mitosis. Aurora B kinase, a CPC subunit, sustains chromosome bi-orientation and the spindle assembly checkpoint (SAC). Here, we characterize the small molecule 5-iodotubercidin (5-ITu) as a potent Haspin inhibitor. In vitro, 5-ITu potently inhibited Haspin but not Aurora B. Consistently, 5-ITu counteracted the centromeric localization of the CPC without affecting the bulk of Aurora B activity in HeLa cells. Mislocalization of Aurora B correlated with dephosphorylation of CENP-A and Hec1 and SAC override at high nocodazole concentrations. 5-ITu also impaired kinetochore recruitment of Bub1 and BubR1 kinases, and this effect was reversed by concomitant inhibition of phosphatase activity. Forcing localization of Aurora B to centromeres in 5-ITu also restored Bub1 and BubR1 localization but failed to rescue the SAC override. This result suggests that a target of 5-ITu, possibly Haspin itself, may further contribute to SAC signaling downstream of Aurora B.

Sign in / Sign up

Export Citation Format

Share Document