Filter and export

Publications

What is a Publication?
62 Publications visible to you, out of a total of 62
Impact of Fibrinogen, Fibrin Thrombi, and Thrombin on Cancer Cell Extravasation Using In Vitro Microvascular Networks

Abstract

Not specified

Authors: Emmanouil Angelidakis, Sophia Chen, Shun Zhang, Zhengpeng Wan, Roger D. Kamm, Sarah E. Shelton

Date Published: 1st May 2023

Publication Type: Journal

Chemo-mechanical diffusion waves explain collective dynamics of immune cell podosomes

Abstract

Not specified

Authors: Ze Gong, Koen van den Dries, Rodrigo A. Migueles-Ramírez, Paul W. Wiseman, Alessandra Cambi, Vivek B. Shenoy

Date Published: 1st May 2023

Publication Type: Journal

Molecular origins of mutational spectra produced by the environmental carcinogen N-nitrosodimethylamine and S(N)1 chemotherapeutic agents.

Abstract (Expand)

DNA-methylating environmental carcinogens such as N-nitrosodimethylamine (NDMA) and certain alkylators used in chemotherapy form O (6)-methylguanine (m6G) as a functionally critical intermediate. NDMA … is a multi-organ carcinogen found in contaminated water, polluted air, preserved foods, tobacco products, and many pharmaceuticals. Only ten weeks after exposure to NDMA, neonatally-treated mice experienced elevated mutation frequencies in liver, lung and kidney of approximately 35-fold, 4-fold and 2-fold, respectively. High-resolution mutational spectra (HRMS) of liver and lung revealed distinctive patterns dominated by GC-->AT mutations in 5'-Pu-G-3' contexts, very similar to human COSMIC mutational signature SBS11. Commonly associated with alkylation damage, SBS11 appears in cancers treated with the DNA alkylator temozolomide (TMZ). When cells derived from the mice were treated with TMZ, N-methyl-N-nitrosourea, and streptozotocin (two other therapeutic methylating agents), all displayed NDMA-like HRMS, indicating mechanistically convergent mutational processes. The role of m6G in shaping the mutational spectrum of NDMA was probed by removing MGMT, the main cellular defense against m6G. MGMT-deficient mice displayed a strikingly enhanced mutant frequency, but identical HRMS, indicating that the mutational properties of these alkylators is likely owed to sequence-specific DNA binding. In sum, the HRMS of m6G-forming agents constitute an early-onset biomarker of exposure to DNA methylating carcinogens and drugs.

Authors: A. L. Armijo, P. Thongararm, B. I. Fedeles, J. Yau, J. E. Kay, J. J. Corrigan, M. Chancharoen, S. Chawanthayatham, L. D. Samson, S. E. Carrasco, B. P. Engelward, J. G. Fox, R. G. Croy, J. M. Essigmann

Date Published: 31st Mar 2023

Publication Type: Journal

Interaction of N-nitrosamines with binuclear copper complexes for luminescent detection.

Abstract (Expand)

Cu(I) from tetrakis(acetonitrile)copper(I) hexafluorophosphate ([Cu(MeCN)(4)]PF(6)) was complexed with five structurally related phosphines containing N-heterocycles. The interactions between the … resulting complexes and some N-nitrosamines were studied using X-ray crystallography as well as emission spectroscopy. Upon complexation, three phosphine ligands bridge two Cu(I) centers to give paddlewheel type structures that displayed a range of emission wavelengths spanning the visible region. N-Nitrosodimethylamine (NDMA) was shown to coordinate to one of the two copper centers in some of the paddlewheel complexes in the solid state and this interaction also quenches their emissions in solution. The influence of the weakly coordinating anion on crystal and spectroscopic properties of one of the paddlewheel complexes was also examined using tetrakis(acetonitrile)copper(I) perchlorate ([Cu(MeCN)(4)]ClO(4)) as an alternative Cu(I) source. Similarly, copper(II) perchlorate hexahydrate (Cu(ClO(4))(2).6H(2)O) was used for complexation to observe the impact of metal oxidation state on the two aforementioned properties. Lastly, the spectroscopic properties of the complex between Ph(2)P(1-Isoquinoline) and Cu(I) was shown to exhibit solvent dependence when the counterion is ClO(4)(-). These Cu(I) complexes are bench stable solids and may be useful materials for developing a fluorescence based detection method for N-nitrosamines.

Authors: H. Feng, S. L. Luo, R. G. Croy, J. M. Essigmann, T. M. Swager

Date Published: 7th Mar 2023

Publication Type: Journal

Benthic Fluxes of Fluorescent Dissolved Organic Material, Salt, and Heat Measured by Multiple-Sensor Aquatic Eddy Covariance.

Abstract (Expand)

Aquatic eddy covariance (AEC) is an in situ technique for measuring fluxes in marine and freshwater systems that is based on the covariance of velocity and concentration measurements. To date, AEC has … mainly been applied to the measurement of benthic oxygen fluxes. Here, development of a fast multiple-channel sensor enables the use of AEC for measurement of benthic fluxes of fluorescent material, salt, and heat at three distinct sites in Massachusetts, USA, including the Connecticut River, the Concord River, and Upper Mystic Lake. Benthic fluxes of salt, useful as a tracer for groundwater input (submarine groundwater discharge), were consistent with independent measurements made with seepage meters. Eddy fluxes of heat were consistent with the balance of incoming solar radiation and thermal conduction at the sediment surface. Benthic eddy fluxes of fluorescent dissolved organic material (FDOM) revealed a substantial net downward flux in the humic-rich Concord River, suggesting that microbial consumption of dissolved organic carbon in the sediment was significant. Simultaneous measurement of several fluxes expands the utility of AEC as a biogeochemical tool while enabling checks for mutual consistency among data channels.

Authors: I. H. Hu, H. F. Hemond

Date Published: 20th Nov 2022

Publication Type: Journal

Interstitial flow promotes the formation of functional microvascular networks in vitro through upregulation of matrix metalloproteinase-2.

Abstract (Expand)

Self-organized microvascular networks (MVNs) have become key to the development of many microphysiological models. However, the self-organizing nature of this process combined with variations between … types or batches of endothelial cells (ECs) often lead to inconsistency or failure to form functional MVNs. Since interstitial flow (IF) has been reported to play a beneficial role in angiogenesis, vasculogenesis, and 3D capillary morphogenesis, we systematically investigated the role IF plays during neovessel formation in a customized single channel microfluidic chip for which IF has been fully characterized. Compared to static conditions, MVNs formed under IF have higher vessel density and diameters and greater network perfusability. Through a series of inhibitory experiments, we demonstrated that IF treatment improves vasculogenesis by ECs through upregulation of matrix metalloproteinase-2 (MMP-2). We then successfully implemented a novel strategy involving the interplay between IF and MMP-2 inhibitor to regulate morphological parameters of the self-organized MVNs, with vascular permeability and perfusability well maintained. The revealed mechanism and proposed methodology were further validated with a brain MVN model. Our findings and methods have the potential to be widely utilized to boost the development of various organotypic MVNs and could be incorporated into related bioengineering applications where perfusable vasculature is desired.

Authors: S. Zhang, Z. Wan, G. Pavlou, A. X. Zhong, L. Xu, R. D. Kamm

Date Published: 21st Oct 2022

Publication Type: Journal

Novel In Vivo CometChip Reveals NDMA-Induced DNA Damage and Repair in Multiple Mouse Tissues.

Abstract (Expand)

The comet assay is a versatile assay for detecting DNA damage in eukaryotic cells. The assay can measure the levels of various types of damage, including DNA strand breaks, abasic sites and alkali-sensitive … sites. Furthermore, the assay can also be modified to include purified DNA glycosylases so that alkylated and oxidized bases can be detected. The CometChip is a higher throughput version of the traditional comet assay and has been used to study cultured cells. Here, we have tested its utility for studies of DNA damage present in vivo. We show that the CometChip is effective in detecting DNA damage in multiple tissues of mice exposed to the direct-acting methylating agent methylmethane sulfonate (MMS) and to the metabolically activated methylating agent N-nitrosodimethylamine (NDMA), which has been found to contaminate food, water, and drugs. Specifically, results from MMS-exposed mice demonstrate that DNA damage can be detected in cells from liver, lung, kidney, pancreas, brain and spleen. Results with NDMA show that DNA damage is detectable in metabolically competent tissues (liver, lung, and kidney), and that DNA repair in vivo can be monitored over time. Additionally, it was found that DNA damage persists for many days after exposure. Furthermore, glycosylases were successfully incorporated into the assay to reveal the presence of damaged bases. Overall, this work demonstrates the efficacy of the in vivo CometChip and reveals new insights into the formation and repair of DNA damage caused by MMS and NDMA.

Authors: N. A. Owiti, J. J. Corrigan, L. J. Pribyl, J. E. Kay, B. P. Engelward

Date Published: 4th Oct 2022

Publication Type: Journal

Powered by
 (v.1.15.1)
About FAIRDOM | About FAIRDOM-SEEK | Funding and Programmes | Credits
Copyright © 2008 - 2024 The University of Manchester and HITS gGmbH