Research and Publications - Department of Chemical & Biological Engineering
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Browsing Research and Publications - Department of Chemical & Biological Engineering by Subject "ACTIVATION"
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Item Accessing the main-group metal formyl scaffold through CO-activation in beryllium hydride complexes(Nature Portfolio, 2022) Hadlington, Terrance J.; Szilvasi, Tibor; Technical University of Munich; University of Alabama TuscaloosaCarbon monoxide (CO) is an indispensable C1 building block. For decades this abundant gas has been employed in hydroformylation and Pausen-Khand catalysis, amongst many related chemistries, where a single, non-coupled CO fragment is delivered to an organic molecule. Despite this, organometallic species which react with CO to yield C1 products remain rare, and are elusive for main group metal complexes. Here, we describe a range of amido-beryllium hydride complexes, and demonstrate their reactivity towards CO, in its mono-insertion into the Be-H bonds of these species. The small radius of the Be2+ ion in conjunction with the non-innocent pendant phosphine moiety of the developed ligands leads to a unique beryllium formyl complex with an ylidic P-C-CO fragment, whereby the carbon centre, remarkably, datively binds Be. This, alongside reactivity toward carbon dioxide, sheds light on the insertion chemistry of the Be-H bond, complimenting the long-known chemistry of the heavier Alkaline Earth hydrides. Stoichiometric carbon monoxide insertion processes leading to metal-formyl complexes are scarce, even for transition metals. Here, light is shed on the underexplored chemistry of beryllium hydrides leading to a stable example of a main group metal-formyl complex.Item Biomaterial Scaffolds as Pre-metastatic Niche Mimics Systemically Alter the Primary Tumor and Tumor Microenvironment(Wiley, 2018) Aguado, Brian A.; Hartfield, Rachel M.; Bushnell, Grace G.; Decker, Joseph T.; Azarin, Samira M.; Nanavati, Dhaval; Schipma, Matthew J.; Rao, Shreyas S.; Oakes, Robert S.; Zhang, Yining; Jeruss, Jacqueline S.; Shea, Lonnie D.; Northwestern University; University of Michigan; University of Alabama TuscaloosaPrimary tumor (PT) immune cells and pre-metastatic niche (PMN) sites are critical to metastasis. Recently, synthetic biomaterial scaffolds used as PMN mimics are shown to capture both immune and metastatic tumor cells. Herein, studies are performed to investigate whether the scaffold-mediated redirection of immune and tumor cells would alter the primary tumor microenvironment (TME). Transcriptomic analysis of PT cells from scaffold-implanted and mock-surgery mice identifies differentially regulated pathways relevant to invasion and metastasis progression. Transcriptomic differences are hypothesized to result from scaffold-mediated modulations of immune cell trafficking and phenotype in the TME. Culturing tumor cells with conditioned media generated from PT immune cells of scaffold-implanted mice decrease invasion in vitro more than two-fold relative to mock surgery controls and reduce activity of invasion-promoting transcription factors. Secretomic characterization of the conditioned media delineates interactions between immune cells in the TME and tumor cells, showing an increase in the pan-metastasis inhibitor decorin and a concomitant decrease in invasion-promoting chemokine (C-C motif) ligand 2 (CCL2) in scaffold-implanted mice. Flow cytometric and transcriptomic profiling of PT immune cells identify phenotypically distinct tumor-associated macrophages (TAMs) in scaffold-implanted mice, which may contribute to an invasion-suppressive TME. Taken together, this study demonstrates biomaterial scaffolds systemically influence metastatic progression through manipulation of the TME.Item Endoplasmic reticulum stress impairment in the spinal dorsal horn of a neuropathic pain model(Nature Portfolio, 2015) Zhang, Enji; Yi, Min-Hee; Shin, Nara; Baek, Hyunjung; Kim, Sena; Kim, Eunjee; Kwon, Kisang; Lee, Sunyeul; Kim, Hyun-Woo; Bae, Yong Chul; Kim, Yonghyun; Kwon, O. -Yu; Lee, Won Hyung; Kim, Dong Woon; Chungnam National University; Chungnam National University Hospital; Kyungpook National University; Yanbian University; University of Alabama TuscaloosaEndoplasmic reticulum (ER) stress has been implicated in neurodegenerative diseases, but its role in neuropathic pain remains unclear. In this study, we examined the ER stress and the unfolded protein response (UPR) activation in a L5 spinal nerve ligation (SNL)-induced rat neuropathic pain model. SNL-induced neuropathic pain was assessed behaviorally using the CatWalk system, and histologically with microglial activation in the dorsal spinal horn. L5 SNL induced BIP upregulation in the neuron of superficial laminae of dorsal spinal horn. It also increased the level of ATF6 and intracellular localization into the nuclei in the neurons. Moreover, spliced XBP1 was also markedly elevated in the ipsilateral spinal dorsal horn. The PERK-elF2 pathway was activated in astrocytes of the spinal dorsal horn in the SNL model. In addition, electron microscopy revealed the presence of swollen cisternae in the dorsal spinal cord after SNL. Additionally, inhibition of the ATF6 pathway by intrathecal treatment with ATF6 siRNA reduced pain behaviors and BIP expression in the dorsal horn. The results suggest that ER stress might be involved in the induction and maintenance of neuropathic pain. Furthermore, a disturbance in UPR signaling may render the spinal neurons vulnerable to peripheral nerve injury or neuropathic pain stimuli.