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Problems In Embalming: Cyanide Poisoning, Rebecca Majus 2017 Southern Illinois University Carbondale

Problems In Embalming: Cyanide Poisoning, Rebecca Majus

ASA Multidisciplinary Research Symposium

To inform funeral professionals, or anyone interested, what cyanide poisoning is, how death from it occurs, how to detect it in postmortem remains, how it poses a problem for embalmers, and what embalming techniques can be used to treat it.


Jnks Function As Cdk4-Activating Kinases By Phosphorylating Cdk4 And P21, B. Colleoni, S. Paternot, J. M. Pita, X. Bisteau, K. Coulonval, Roger J. Davis, E. Raspe, P. P. Roger 2017 Université Libre de Bruxelles, Belgium

Jnks Function As Cdk4-Activating Kinases By Phosphorylating Cdk4 And P21, B. Colleoni, S. Paternot, J. M. Pita, X. Bisteau, K. Coulonval, Roger J. Davis, E. Raspe, P. P. Roger

Open Access Articles

Cyclin D-CDK4/6 are the first cyclin-dependent kinase (CDK) complexes to be activated by mitogenic/oncogenic pathways. They have a central role in the cell multiplication decision and in its deregulation in cancer cells. We identified T172 phosphorylation of CDK4 rather than cyclin D accumulation as the distinctly regulated step determining CDK4 activation. This finding challenges the view that the only identified metazoan CDK-activating kinase, cyclin H-CDK7-Mat1 (CAK), which is constitutively active, is responsible for the activating phosphorylation of all cell cycle CDKs. We previously showed that T172 phosphorylation of CDK4 is conditioned by an adjacent proline (P173), which is ...


5-Vinylphosphonate Improves Tissue Accumulation And Efficacy Of Conjugated Sirnas In Vivo, Reka A. Haraszti, Loic Roux, Andrew H. Coles, Anton A. Turanov, Julia F. Alterman, Dimas Echeverria, Bruno M. D. C. Godinho, Neil Aronin, Anastasia Khvorova 2017 University of Massachusetts Medical School

5-Vinylphosphonate Improves Tissue Accumulation And Efficacy Of Conjugated Sirnas In Vivo, Reka A. Haraszti, Loic Roux, Andrew H. Coles, Anton A. Turanov, Julia F. Alterman, Dimas Echeverria, Bruno M. D. C. Godinho, Neil Aronin, Anastasia Khvorova

Open Access Articles

5-Vinylphosphonate modification of siRNAs protects them from phosphatases, and improves silencing activity. Here, we show that 5-vinylphosphonate confers novel properties to siRNAs. Specifically, 5-vinylphosphonate (i) increases siRNA accumulation in tissues, (ii) extends duration of silencing in multiple organs and (iii) protects siRNAs from 5-to-3 exonucleases. Delivery of conjugated siRNAs requires extensive chemical modifications to achieve stability in vivo. Because chemically modified siRNAs are poor substrates for phosphorylation by kinases, and 5-phosphate is required for loading into RNA-induced silencing complex, the synthetic addition of a 5-phosphate on a fully modified siRNA guide strand is expected to be beneficial. Here, we show ...


Crystal Structure Of Apobec3a Bound To Single-Stranded Dna Reveals Structural Basis For Cytidine Deamination And Specificity, Takahide Kouno, Tania V. Silvas, Brendan J. Hilbert, Shivender Shandilya, Markus-Frederik Bohn, Brian A. Kelch, William E. Royer, Mohan Somasundaran, Nese Kurt Yilmaz, Hiroshi Matsuo, Celia A. Schiffer 2017 University of Massachusetts Medical School

Crystal Structure Of Apobec3a Bound To Single-Stranded Dna Reveals Structural Basis For Cytidine Deamination And Specificity, Takahide Kouno, Tania V. Silvas, Brendan J. Hilbert, Shivender Shandilya, Markus-Frederik Bohn, Brian A. Kelch, William E. Royer, Mohan Somasundaran, Nese Kurt Yilmaz, Hiroshi Matsuo, Celia A. Schiffer

Celia A. Schiffer

Nucleic acid editing enzymes are essential components of the immune system that lethally mutate viral pathogens and somatically mutate immunoglobulins, and contribute to the diversification and lethality of cancers. Among these enzymes are the seven human APOBEC3 deoxycytidine deaminases, each with unique target sequence specificity and subcellular localization. While the enzymology and biological consequences have been extensively studied, the mechanism by which APOBEC3s recognize and edit DNA remains elusive. Here we present the crystal structure of a complex of a cytidine deaminase with ssDNA bound in the active site at 2.2 A. This structure not only visualizes the active ...


Dengue Virus Ns2b/Ns3 Protease Inhibitors Exploiting The Prime Side, Kuan-Hung Lin, Akbar Ali, Linah Rusere, Djade I. Soumana, Nese Kurt Yilmaz, Celia A. Schiffer 2017 University of Massachusetts Medical School

Dengue Virus Ns2b/Ns3 Protease Inhibitors Exploiting The Prime Side, Kuan-Hung Lin, Akbar Ali, Linah Rusere, Djade I. Soumana, Nese Kurt Yilmaz, Celia A. Schiffer

Celia A. Schiffer

The mosquito-transmitted dengue virus (DENV) infects millions of people in tropical and subtropical regions. Maturation of DENV particles requires proper cleavage of the viral polyprotein, including processing of 8 of the 13 substrate cleavage sites by dengue virus NS2B/NS3 protease. With no available direct-acting antiviral targeting DENV, NS2/NS3 protease is a promising target for inhibitor design. Current design efforts focus on the nonprime side of the DENV protease active site, resulting in highly hydrophilic and nonspecific scaffolds. However, the prime side also significantly modulates DENV protease binding affinity, as revealed by engineering the binding loop of aprotinin, a ...


Interdependence Of Inhibitor Recognition In Hiv-1 Protease, Janet L. Paulsen, Florian Leidner, Debra A. Ragland, Nese Kurt Yilmaz, Celia A. Schiffer 2017 University of Massachusetts Medical School

Interdependence Of Inhibitor Recognition In Hiv-1 Protease, Janet L. Paulsen, Florian Leidner, Debra A. Ragland, Nese Kurt Yilmaz, Celia A. Schiffer

Celia A. Schiffer

Molecular recognition is a highly interdependent process. Subsite couplings within the active site of proteases are most often revealed through conditional amino acid preferences in substrate recognition. However, the potential effect of these couplings on inhibition and thus inhibitor design is largely unexplored. The present study examines the interdependency of subsites in HIV-1 protease using a focused library of protease inhibitors, to aid in future inhibitor design. Previously a series of darunavir (DRV) analogs was designed to systematically probe the S1' and S2' subsites. Co-crystal structures of these analogs with HIV-1 protease provide the ideal opportunity to probe subsite interdependency ...


Diverse Stimuli Engage Different Neutrophil Extracellular Trap Pathways, Elaine F. Kenny, Alf Herzig, Renate Krüger, Aaron Muth, Santanu Mondal, Paul R. Thompson, Volker Brinkmann, Horst Von Bernuth, Arturo Zychlinsky 2017 Max Planck Institute for Infection Biology

Diverse Stimuli Engage Different Neutrophil Extracellular Trap Pathways, Elaine F. Kenny, Alf Herzig, Renate Krüger, Aaron Muth, Santanu Mondal, Paul R. Thompson, Volker Brinkmann, Horst Von Bernuth, Arturo Zychlinsky

Thompson Lab Publications

Neutrophils release neutrophil extracellular traps (NETs) which ensnare pathogens and have pathogenic functions in diverse diseases. We examined the NETosis pathways induced by five stimuli; PMA, the calcium ionophore A23187, nigericin, Candida albicans and Group B Streptococcus. We studied NET production in neutrophils from healthy donors with inhibitors of molecules crucial to PMA induced NETs including protein kinase C, calcium, reactive oxygen species, the enzymes myeloperoxidase (MPO) and neutrophil elastase. Additionally, neutrophils from chronic granulomatous disease patients, carrying mutations in the NADPH oxidase complex or a MPO-deficient patient were examined. We show that PMA, C. albicans and GBS use a ...


Role Of Peptidylarginine Deiminase 2 (Pad2) In Mammary Carcinoma Cell Migration, Sachi Horibata, Katherine E. Rogers, David Sadegh, Lynne J. Anguish, John L. McElwee, Pragya Shah, Paul R. Thompson, Scott A. Coonrod 2017 Cornell University

Role Of Peptidylarginine Deiminase 2 (Pad2) In Mammary Carcinoma Cell Migration, Sachi Horibata, Katherine E. Rogers, David Sadegh, Lynne J. Anguish, John L. Mcelwee, Pragya Shah, Paul R. Thompson, Scott A. Coonrod

Thompson Lab Publications

BACKGROUND: Penetration of the mammary gland basement membrane by cancer cells is a crucial first step in tumor invasion. Using a mouse model of ductal carcinoma in situ, we previously found that inhibition of peptidylarginine deiminase 2 (PAD2, aka PADI2) activity appears to maintain basement membrane integrity in xenograft tumors. The goal of this investigation was to gain insight into the mechanisms by which PAD2 mediates this process.

METHODS: For our study, we modulated PAD2 activity in mammary ductal carcinoma cells by lentiviral shRNA-mediated depletion, lentiviral-mediated PAD2 overexpression, or PAD inhibition and explored the effects of these treatments on changes ...


Theaflavin-3, 3'-Digallate Decreases Human Ovarian Carcinoma Ovcar-3 Cell-Induced Angiogenesis Via Akt And Notch-1 Pathways, Not Via Mapk Pathways, Ying Gao, Gary O. Rankin, Youying Tu, Yi Charlie Chen 2017 Marshall University

Theaflavin-3, 3'-Digallate Decreases Human Ovarian Carcinoma Ovcar-3 Cell-Induced Angiogenesis Via Akt And Notch-1 Pathways, Not Via Mapk Pathways, Ying Gao, Gary O. Rankin, Youying Tu, Yi Charlie Chen

Gary O. Rankin

Theaflavin-3, 3'-digallate (TF3) is a black tea polyphenol produced from polymerization and oxidization of the green tea ployphenols epicatechin gallate and (-)-epigallocatechin-3-gallate (EGCG) during fermentation of fresh tea leaves. TF3 has been reported to have anticancer properties. However, the effect of TF3 on tumor angiogenesis and the underlying mechanisms are not clear. In the present study, TF3 was verified to inhibit tumor angiogenesis. Compared with EGCG, TF3 was more potent. TF3 inhibited human ovarian carcinoma OVCAR-3 cell-induced angiogenesis in human umbilical vein endothelial cell model and in chick chorioallantoic membrane model. TF3 reduced tumor angiogenesis by downregulating HIF-1α and ...


Interdependence Of Inhibitor Recognition In Hiv-1 Protease, Janet L. Paulsen, Florian Leidner, Debra A. Ragland, Nese Kurt Yilmaz, Celia A. Schiffer 2017 University of Massachusetts Medical School

Interdependence Of Inhibitor Recognition In Hiv-1 Protease, Janet L. Paulsen, Florian Leidner, Debra A. Ragland, Nese Kurt Yilmaz, Celia A. Schiffer

University of Massachusetts Medical School Faculty Publications

Molecular recognition is a highly interdependent process. Subsite couplings within the active site of proteases are most often revealed through conditional amino acid preferences in substrate recognition. However, the potential effect of these couplings on inhibition and thus inhibitor design is largely unexplored. The present study examines the interdependency of subsites in HIV-1 protease using a focused library of protease inhibitors, to aid in future inhibitor design. Previously a series of darunavir (DRV) analogs was designed to systematically probe the S1' and S2' subsites. Co-crystal structures of these analogs with HIV-1 protease provide the ideal opportunity to probe subsite interdependency ...


Chloramidine/Bisindolylmaleimide-I-Mediated Inhibition Of Exosome And Microvesicle Release And Enhanced Efficacy Of Cancer Chemotherapy, Uchini S. Kosgodage, Rita P. Trindade, Paul R. Thompson, Jameel M. Inal, Sigrun Lange 2017 London Metropolitan University

Chloramidine/Bisindolylmaleimide-I-Mediated Inhibition Of Exosome And Microvesicle Release And Enhanced Efficacy Of Cancer Chemotherapy, Uchini S. Kosgodage, Rita P. Trindade, Paul R. Thompson, Jameel M. Inal, Sigrun Lange

Open Access Articles

Microvesicle (MV) release from tumour cells influences drug retention, contributing to cancer drug resistance. Strategically regulating MV release may increase drug retention within cancer cells and allow for lower doses of chemotherapeutic drugs. The contribution of exosomes to drug retention still remains unknown. Potential exosome and MV (EMV) biogenesis inhibitors, tested on human prostate cancer (PC3) cells for their capacity to inhibit EMV release, were also tested on PC3 and MCF-7 (breast cancer) cells for improving chemotherapy. Agents inhibiting EMV release most significantly, whilst maintaining cell viability, were chloramidine (Cl-amidine; 50 microM) and bisindolylmaleimide-I (10 microM). Apoptosis mediated by the ...


A Chemoenzymatic Approach For Synthesizing Polymeric Hemoglobin, Johann P. Sigurjonsson 2017 Western Washington University

A Chemoenzymatic Approach For Synthesizing Polymeric Hemoglobin, Johann P. Sigurjonsson

Graduate Student Conference

Polymerized hemoglobin (Hb) molecules have been shown to decrease previously observed adverse events associated with the administration of cell-free hemoglobin. To create these polymers, a method will be developed which employs the site specific ligation reaction of the sortase A enzyme from S. aureus. An Hb mutant (“αcpβ“) previously developed in our lab has been further modified by adding either the sortase recognition sequence, LPXTG, to the C-terminus of the α-subunit (s-αcpβ), or a tetraglycine motif, GGGG, to the N-terminus (n-αcpβ). Three types of sortase mediated ligation (SML) will be employed in this study. First, we will attempt to ligate ...


Kinetic Studies Of Dna Repair Enzyme Alkbh2, Michael R. Vittori 2017 University of Rhode Island

Kinetic Studies Of Dna Repair Enzyme Alkbh2, Michael R. Vittori

Senior Honors Projects

The genomes of living organisms are under constant bombardment from various sources, including chemical modification stemming from processes within the organisms themselves or from exogenous agents, and from radiation. These sources of genomic damage may induce structural changes in the genome’s most basic functional units, the nucleotides that comprise DNA. Damage to an organism’s DNA may result in the production of dysfunctional or nonfunctional proteins. Failure to repair such damage may result in the compounding of successive mutations within the organism’s genome, the pathogenesis of cancer and various genetic disorders in humans. To ensure their viability, organisms ...


Connecting Energy Metabolism And Neurodegeneration: Pyruvate Kinase And Oxidative Stress, Julia P. Zuercher 2017 College of William and Mary

Connecting Energy Metabolism And Neurodegeneration: Pyruvate Kinase And Oxidative Stress, Julia P. Zuercher

Undergraduate Honors Theses

Pyruvate kinase (PK), an important glycolytic enzyme that catalyzes the final step of glycolysis through an irreversible mechanism to produce energy for the cell, contains nine cysteines, some of which are highly reactive and critical for function. This research sought to develop a protocol to measure quantitatively the functionality of PK under different experimental conditions. Using a three stage, consistent procedure, it was possible to analyze the effects of thiol modification by Ellman’s Reagent (DTNB) and oxidation by hypochlorous acid (HOCl) on PK activity. Results showed that both DTNB and HOCl inhibited activity at high concentrations, which illustrates that ...


Effects Of Nicotine On The Cyp6a8 Gene Promoter Of Drosophila Melanogaster, Leslie M. Stroud 2017 University of Tennessee

Effects Of Nicotine On The Cyp6a8 Gene Promoter Of Drosophila Melanogaster, Leslie M. Stroud

University of Tennessee Honors Thesis Projects

No abstract provided.


Crystal Structure Of Apobec3a Bound To Single-Stranded Dna Reveals Structural Basis For Cytidine Deamination And Specificity, Takahide Kouno, Tania V. Silvas, Brendan J. Hilbert, Shivender Shandilya, Markus-Frederik Bohn, Brian A. Kelch, William E. Royer, Mohan Somasundaran, Nese Kurt Yilmaz, Hiroshi Matsuo, Celia A. Schiffer 2017 University of Massachusetts Medical School

Crystal Structure Of Apobec3a Bound To Single-Stranded Dna Reveals Structural Basis For Cytidine Deamination And Specificity, Takahide Kouno, Tania V. Silvas, Brendan J. Hilbert, Shivender Shandilya, Markus-Frederik Bohn, Brian A. Kelch, William E. Royer, Mohan Somasundaran, Nese Kurt Yilmaz, Hiroshi Matsuo, Celia A. Schiffer

University of Massachusetts Medical School Faculty Publications

Nucleic acid editing enzymes are essential components of the immune system that lethally mutate viral pathogens and somatically mutate immunoglobulins, and contribute to the diversification and lethality of cancers. Among these enzymes are the seven human APOBEC3 deoxycytidine deaminases, each with unique target sequence specificity and subcellular localization. While the enzymology and biological consequences have been extensively studied, the mechanism by which APOBEC3s recognize and edit DNA remains elusive. Here we present the crystal structure of a complex of a cytidine deaminase with ssDNA bound in the active site at 2.2 A. This structure not only visualizes the active ...


Dengue Virus Ns2b/Ns3 Protease Inhibitors Exploiting The Prime Side, Kuan-Hung Lin, Akbar Ali, Linah Rusere, Djade I. Soumana, Nese Kurt Yilmaz, Celia A. Schiffer 2017 University of Massachusetts Medical School

Dengue Virus Ns2b/Ns3 Protease Inhibitors Exploiting The Prime Side, Kuan-Hung Lin, Akbar Ali, Linah Rusere, Djade I. Soumana, Nese Kurt Yilmaz, Celia A. Schiffer

University of Massachusetts Medical School Faculty Publications

The mosquito-transmitted dengue virus (DENV) infects millions of people in tropical and subtropical regions. Maturation of DENV particles requires proper cleavage of the viral polyprotein, including processing of 8 of the 13 substrate cleavage sites by dengue virus NS2B/NS3 protease. With no available direct-acting antiviral targeting DENV, NS2/NS3 protease is a promising target for inhibitor design. Current design efforts focus on the nonprime side of the DENV protease active site, resulting in highly hydrophilic and nonspecific scaffolds. However, the prime side also significantly modulates DENV protease binding affinity, as revealed by engineering the binding loop of aprotinin, a ...


Kat-Independent Gene Regulation By Tip60 Promotes Esc Self-Renewal But Not Pluripotency, Diwash Acharya, Sarah J. Hainer, Yeonsoo Yoon, Feng Wang, Ingolf Bach, Jaime A. Rivera-Perez, Thomas G. Fazzio 2017 University of Massachusetts Medical School Worcester

Kat-Independent Gene Regulation By Tip60 Promotes Esc Self-Renewal But Not Pluripotency, Diwash Acharya, Sarah J. Hainer, Yeonsoo Yoon, Feng Wang, Ingolf Bach, Jaime A. Rivera-Perez, Thomas G. Fazzio

Pediatric Publications and Presentations

Although histone-modifying enzymes are generally assumed to function in a manner dependent on their enzymatic activities, this assumption remains untested for many factors. Here, we show that the Tip60 (Kat5) lysine acetyltransferase (KAT), which is essential for embryonic stem cell (ESC) self-renewal and pre-implantation development, performs these functions independently of its KAT activity. Unlike ESCs depleted of Tip60, KAT-deficient ESCs exhibited minimal alterations in gene expression, chromatin accessibility at Tip60 binding sites, and self-renewal, thus demonstrating a critical KAT-independent role of Tip60 in ESC maintenance. In contrast, KAT-deficient ESCs exhibited impaired differentiation into mesoderm and endoderm, demonstrating a KAT-dependent function ...


Compromised External Validity: Federally Produced Cannabis Does Not Reflect Legal Markets, Daniela Vergara, L. Cinnamon Bidwell, Kent E. Hutchison, Nolan C. Kane, Reggie Gaudino, Anthony Torres, Gary Du, Travis C. Ruthenburg, Kymron deCesare, Donald P. Land 2017 University of Colorado Boulder

Compromised External Validity: Federally Produced Cannabis Does Not Reflect Legal Markets, Daniela Vergara, L. Cinnamon Bidwell, Kent E. Hutchison, Nolan C. Kane, Reggie Gaudino, Anthony Torres, Gary Du, Travis C. Ruthenburg, Kymron Decesare, Donald P. Land

University Libraries Open Access Fund Supported Publications

As the most widely used illicit drug worldwide, and as a source of numerous under-studied pharmacologically-active compounds, a precise understanding of variability in psychological and physiological effects of Cannabis varieties is essential. The National Institute on Drug Abuse (NIDA) is designated as the sole legal producer of Cannabis for use in US research studies. We sought to compare the chemical profiles of Cannabis varieties that are available to consumers in states that have statelegalized use versus what is available to researchers interested in studying the plant and its effects. Our results demonstrate that the federally-produced Cannabis has significantly less variety ...


Structural Studies On Hiv-1 Protease To Investigate Correlation Between Conformational Dynamics And Drug-Resistance, Rowan Brothers 2017 Georgia State University

Structural Studies On Hiv-1 Protease To Investigate Correlation Between Conformational Dynamics And Drug-Resistance, Rowan Brothers

Georgia State Undergraduate Research Conference

No abstract provided.


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