Augmentative and Alternative Communication Devices and Their Effectiveness as Elements of Early Intervention

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West-Nile virus replicon particles infect 293T cells expressing DC-SIGNR

West-Nile virus (WNV) is an arbovirus usually transmitted to humans via a mosquito vector. Infections commonly result in febrile symptoms while rare severe neuroinvasive cases may result in encephalitis or meningitis. Studies have shown that WNV infection efficiency is enhanced by expression of DC-SIGNR on target cells, which normally do not express DC-SIGNR. To investigate WNV tropism, we established 293T kidney epithelial cell lines that stably express vector, DC-SIGNR and mutants of DC-SIGNR that lack the entire carbohydrate-recognition domain (CRD) or lack the C-terminal half of the CRD. We demonstrate successful surface expression of DC-SIGNR and its mutants from stablytransfected 293T cells, but not vector-transfected 293T cells. Further, we show that monoclonal antibody 120604 which binds specifically to the DC-SIGNR CRD binds to DCSIGNR expressing 293T cells, but not to vector nor any of the DC-SIGNR mutants expressing cells. Virus replicon particles (VRPs), replication-incompetent viral particles containing necessary structural proteins for infection and a viral plasmid including a GFP reporter are used to safely and conveniently study viral entry. Entry assays using WNV (NY99) VRPs as well as a variant of WNV (NY99) which contains the beta-lactamase enzyme show significant entry into DC-SIGNR expressing cell lines, but not in controls that do not express DC-SIGNR. Additionally, we show that WNV VRPs do not enter DC-SIGNR expressing cells that lack the CRD or the C-terminal half of the CRD suggesting that the Cterminal half of the CRD is required for successful entry of WNV via DC-SIGNR. Future experiments may be able to shed light on which amino acids are required for entryhttps://openriver.winona.edu/urc2018/1057/thumbnail.jp

Farm Legal Series: Choosing the Right Business Entity, 2020

This publication may not reflect current laws, scientific knowledge or recommendations. Current information about farm legal issues is available from the University of Minnesota Extension: www.extension.umn.ed

Farm Legal Series: Tax Considerations in Liquidations and Reorganizations, 2020

This publication may not reflect current laws, scientific knowledge or recommendations. Current information about farm legal issues is available from the University of Minnesota Extension: www.extension.umn.ed

Farm Legal Series, 2020

This publication may not reflect current laws, scientific knowledge or recommendations. Current information about farm legal issues is available from the University of Minnesota Extension: www.extension.umn.ed

West-Nile virus replicon particle entry requires the C-terminal half of the carbohydraterecognition domain of the Dendritic cell-specific ICAM-3 grabbing non-integrin related protein

West-Nile virus (WNV) is an arbovirus usually transmitted to humans via a mosquito vector. Infections commonly result in febrile symptoms while rare severe neuroinvasive cases may result in encephalitis or meningitis. Studies have shown that WNV infection efficiency is enhanced by expression of DC-SIGNR on target cells, which normally do not express DC-SIGNR. To investigate WNV tropism, we established 293T kidney epithelial cell lines that stably express vector, DC-SIGNR and mutants of DC-SIGNR that lack the entire carbohydrate-recognition domain (CRD) or lack the C-terminal half of the CRD. We demonstrate successful surface expression of DC-SIGNR and its mutants from stably-transfected 293T cells, but not vector-transfected 293T cells. Further, we show that monoclonal antibody 120604 which binds specifically to the DC-SIGNR CRD binds to DC-SIGNR expressing 293T cells, but not to vector nor any of the DC-SIGNR mutants expressing cells. Virus replicon particles (VRPs), replication-incompetent viral particles containing necessary structural proteins for infection and a viral plasmid including a GFP 19 reporter are used to safely and conveniently study viral entry. Entry assays using WNV (NY99) VRPs as well as a variant of WNV (NY99) which contains the beta-lactamase enzyme show significant entry into DC-SIGNR expressing cell lines, but not in controls that do not express DC-SIGNR. Additionally, we show that WNV VRPs do not enter DC-SIGNR expressing cells that lack the CRD or the C-terminal half of the CRD suggesting that the C-terminal half of the CRD is required for successful entry of WNV via DC-SIGNR. Future experiments may be able to shed light on which amino acids are required for entry

DNA Polymerase and Mismatch Repair Exert Distinct Microsatellite Instability Signatures in Normal and Malignant Human Cells.

Although replication repair deficiency, either by mismatch repair deficiency (MMRD) and/or loss of DNA polymerase proofreading, can cause hypermutation in cancer, microsatellite instability (MSI) is considered a hallmark of MMRD alone. By genome-wide analysis of tumors with germline and somatic deficiencies in replication repair, we reveal a novel association between loss of polymerase proofreading and MSI, especially when both components are lost. Analysis of indels in microsatellites (MS-indels) identified five distinct signatures (MS-sigs). MMRD MS-sigs are dominated by multibase losses, whereas mutant-polymerase MS-sigs contain primarily single-base gains. MS deletions in MMRD tumors depend on the original size of the MS and converge to a preferred length, providing mechanistic insight. Finally, we demonstrate that MS-sigs can be a powerful clinical tool for managing individuals with germline MMRD and replication repair-deficient cancers, as they can detect the replication repair deficiency in normal cells and predict their response to immunotherapy. SIGNIFICANCE: Exome- and genome-wide MSI analysis reveals novel signatures that are uniquely attributed to mismatch repair and DNA polymerase. This provides new mechanistic insight into MS maintenance and can be applied clinically for diagnosis of replication repair deficiency and immunotherapy response prediction.