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Full-Text Articles in Life Sciences

Proteomic Analysis Of The Acidocalcisome, An Organelle Conserved From Bacteria To Human Cells, Guozhong Huang, Paul N. Ulrich, Melissa Storey, Darryl Johnson, Julie Tischer, Javier A. Tovar, Silvia N. J. Moreno, Ron Orlando, Robert Docampo Dec 2014

Proteomic Analysis Of The Acidocalcisome, An Organelle Conserved From Bacteria To Human Cells, Guozhong Huang, Paul N. Ulrich, Melissa Storey, Darryl Johnson, Julie Tischer, Javier A. Tovar, Silvia N. J. Moreno, Ron Orlando, Robert Docampo

Biology Faculty Publications

Acidocalcisomes are acidic organelles present in a diverse range of organisms from bacteria to human cells. In this study acidocalcisomes were purified from the model organism Trypanosoma brucei, and their protein composition was determined by mass spectrometry. The results, along with those that we previously reported, show that acidocalcisomes are rich in pumps and transporters, involved in phosphate and cation homeostasis, and calcium signaling. We validated the acidocalcisome localization of seven new, putative, acidocalcisome proteins (phosphate transporter, vacuolar H+-ATPase subunits a and d, vacuolar iron transporter, zinc transporter, polyamine transporter, and acid phosphatase), confirmed the presence of six previously ...


Recombinant Influenza Virus Carrying The Conserved Domain Of Respiratory Syncytial Virus (Rsv) G Protein Confers Protection Against Rsv Without Inflammatory Disease, Yu-Na Lee, Hye Suk Hwang, Min-Chul Kim, Young-Tae Lee, Min-Kyoung Cho, Young-Man Kwon, Jong Seok Lee, Richard K. Plemper, Sang-Moo Kang Dec 2014

Recombinant Influenza Virus Carrying The Conserved Domain Of Respiratory Syncytial Virus (Rsv) G Protein Confers Protection Against Rsv Without Inflammatory Disease, Yu-Na Lee, Hye Suk Hwang, Min-Chul Kim, Young-Tae Lee, Min-Kyoung Cho, Young-Man Kwon, Jong Seok Lee, Richard K. Plemper, Sang-Moo Kang

Biology Faculty Publications

Respiratory syncytial virus (RSV) is one of the most important causes for viral lower respiratory tract disease in humans. There is no licensed RSV vaccine. Here, we generated recombinant influenza viruses (PR8/RSV. HA-G) carrying the chimeric constructs of hemagglutinin (HA) and central conserved-domains of the RSV G protein. PR8/RSV.HA-G virus showed lower pathogenicity without compromising immunogenicity in mice. Single intranasal inoculation of mice with PR8/RSV.HA-G induced IgG2a isotype dominant antibodies and RSV neutralizing activity. Mice with single intranasal inoculation of PR8/RSV.HA-G were protected against RSV infection as evidenced by significant reduction of lung ...


Hes-Mediated Repression Of Pten In Caenorhabditis Elegans, Han Ting Chou, Raymarie Gomez Vazquez, Kun Wang, Richard Campbell, Gaolin Zheng Milledge, Walter W. Walthall, Casonya Matese Johnson Oct 2014

Hes-Mediated Repression Of Pten In Caenorhabditis Elegans, Han Ting Chou, Raymarie Gomez Vazquez, Kun Wang, Richard Campbell, Gaolin Zheng Milledge, Walter W. Walthall, Casonya Matese Johnson

Biology Faculty Publications

The Hairy/Enhancer-of-Split (HES) group of transcription factors controls embryonic development, often by acting downstream of the Notch signaling pathway; however, little is known about postembryonic roles of these proteins. In Caenorhabditis elegans, the six proteins that make up the REF-1 family are considered to be HES orthologs that act in both Notch dependent and Notch-independent pathways to regulate embryonic events. To further our understanding of how the REF-1 family works to coordinate post-embryonic cellular events, we performed a functional characterization of the REF-1 family member, HLH-25. We show that, after embryogenesis, hlh-25 expression persists throughout every developmental stage, including ...


Cyclodextrin Complexes Of Reduced Bromonoscapine In Guar Gum Microspheres Enhance Colonic Drug Delivery, Jitender Madan, Sushma R. Gundala, Bharat Baruah, Mulpuri Nagaraju, Clayton Yates, Timothy Turner, Vijay Rangari, Donald Hamelberg, Michelle D. Reid, Ritu Aneja Oct 2014

Cyclodextrin Complexes Of Reduced Bromonoscapine In Guar Gum Microspheres Enhance Colonic Drug Delivery, Jitender Madan, Sushma R. Gundala, Bharat Baruah, Mulpuri Nagaraju, Clayton Yates, Timothy Turner, Vijay Rangari, Donald Hamelberg, Michelle D. Reid, Ritu Aneja

Biology Faculty Publications

Here, we report improved solubility and enhanced colonic delivery of reduced bromonoscapine (Red-Br-Nos), a cyclic ether brominated analogue of noscapine, upon encapsulation of its cyclodextrin (CD) complexes in bioresponsive guar gum microspheres (GGM). Phase−solubility analysis suggested that Red-Br-Nos complexed with β-CD and methyl-β-CD in a 1:1 stoichiometry, with a stability constant (Kc) of 2.29 × 103 M−1 and 4.27 × 103 M−1. Fourier transforms infrared spectroscopy indicated entrance of an O−CH2 or OCH3−C6H4−OCH3 moiety of Red-Br-Nos in the β-CD or methyl-β- CD cavity. Furthermore, the cage complex of Red-Br-Nos with β-CD and methyl-β-CD ...


Tlr5-Mediated Sensing Of Gut Microbiota Is Necessary For Antibody Responses To Seasonal Influenza Vaccination, Jason Z. Oh, Rajesh Ravidran, Benoit Chassaing, Frederic A. Carvalho, Mohan S. Madur, Maureen Bower, Paul Hakimpour, Kiran P. Gill, Helder I. Nakaya, Felix Yarovinsky, R. Balfour Sartor, Andrew T. Gewirtz, Bali Pulendran Sep 2014

Tlr5-Mediated Sensing Of Gut Microbiota Is Necessary For Antibody Responses To Seasonal Influenza Vaccination, Jason Z. Oh, Rajesh Ravidran, Benoit Chassaing, Frederic A. Carvalho, Mohan S. Madur, Maureen Bower, Paul Hakimpour, Kiran P. Gill, Helder I. Nakaya, Felix Yarovinsky, R. Balfour Sartor, Andrew T. Gewirtz, Bali Pulendran

Biology Faculty Publications

No abstract provided.


Modulation Of Cytochrome P450 Metabolism And Transport Across Intestinal Epithelial Barrier By Ginger Biophenolics, Rao Mukkavilli, Sushma R. Gundala, Chunhua Yang, Shashikiran Donthamsetty, Guilherme Cantuaria, Gajanan R. Jadhav, Subrahmanyam Vangala, Michelle D. Reid, Ritu Aneja Sep 2014

Modulation Of Cytochrome P450 Metabolism And Transport Across Intestinal Epithelial Barrier By Ginger Biophenolics, Rao Mukkavilli, Sushma R. Gundala, Chunhua Yang, Shashikiran Donthamsetty, Guilherme Cantuaria, Gajanan R. Jadhav, Subrahmanyam Vangala, Michelle D. Reid, Ritu Aneja

Biology Faculty Publications

Natural and complementary therapies in conjunction with mainstream cancer care are steadily gaining popularity. Ginger extract (GE) confers significant health-promoting benefits owing to complex additive and/or synergistic interactions between its bioactive constituents. Recently, we showed that preservation of natural ‘‘milieu’’ confers superior anticancer activity on GE over its constituent phytochemicals, 6-gingerol (6G), 8-gingerol (8G), 10-gingerol (10G) and 6-shogaol (6S), through enterohepatic recirculation. Here we further evaluate and compare the effects of GE and its major bioactive constituents on cytochrome P450 (CYP) enzyme activity in human liver microsomes by monitoring metabolites of CYPspecific substrates using LC/MS/MS detection methods ...


Each Of The Eight Simian Hemorrhagic Fever Virus Minor Structural Proteins Is Functionally Important, Heather A. Vatter, Han Di, Eric F. Donaldson, Ralph S. Baric, Margo A. Brinton Jul 2014

Each Of The Eight Simian Hemorrhagic Fever Virus Minor Structural Proteins Is Functionally Important, Heather A. Vatter, Han Di, Eric F. Donaldson, Ralph S. Baric, Margo A. Brinton

Biology Faculty Publications

The simian hemorrhagic fever virus (SHFV) genome differs from those of other members of the family Arterivirus in encoding two adjacent sets of four minor structural protein open reading frames (ORFs). A stable, full-length, infectious SHFV-LVR cDNA clone was constructed. Virus produced from this clone had replication characteristics similar to those of the parental virus. A subgenomic mRNA was identified for the SHFV ORF previously identified as 2b. As an initial means of analyzing the functional relevance of each of the SHFV minor structural proteins, a set of mutant infectious clones was generated, each with the start codon of one ...


Kifci, A Novel Putative Prognostic Biomarker For Ovarian Adenocarcinomas: Delineating Protein Interaction Networks And Signaling Circuitries, Shrikant Pawar, Shashikiran Donthamsetty, Vaishali Pannu, Padmashree Rida, Angela Ogden, Nathan Bowen, Remus Osan, Guilherme Cantuaria, Ritu Aneja May 2014

Kifci, A Novel Putative Prognostic Biomarker For Ovarian Adenocarcinomas: Delineating Protein Interaction Networks And Signaling Circuitries, Shrikant Pawar, Shashikiran Donthamsetty, Vaishali Pannu, Padmashree Rida, Angela Ogden, Nathan Bowen, Remus Osan, Guilherme Cantuaria, Ritu Aneja

Biology Faculty Publications

Background: Amplified centrosomes in cancers are recently garnering a lot of attention as an emerging hub of diagnostic, prognostic and therapeutic targets. Ovarian adenocarcinomas commonly harbor supernumerary centrosomes that drive chromosomal instability. A centrosome clustering molecule, KIFC1, is indispensable for the viability of extra centrosome-bearing cancer cells, and may underlie progression of ovarian cancers.
Methods: Centrosome amplification in low- and high- grade serous ovarian adenocarcinomas was quantitated employing confocal imaging. KIFC1 expression was analyzed in ovarian tumors using publically-available databases. Associated grade, stage and clinical information from these databases were plotted for KIFC1 gene expression values. Furthermore, interactions and functional ...


Cephalopod Ink: Production, Chemistry, Functions And Applications, Charles D. Derby May 2014

Cephalopod Ink: Production, Chemistry, Functions And Applications, Charles D. Derby

Biology Faculty Publications

One of the most distinctive and defining features of coleoid cephalopods—squid, cuttlefish and octopus—is their inking behavior. Their ink, which is blackened by melanin, but also contains other constituents, has been used by humans in various ways for millennia. This review summarizes our current knowledge of cephalopod ink. Topics include: (1) the production of ink, including the functional organization of the ink sac and funnel organ that produce it; (2) the chemical components of ink, with a focus on the best known of these—melanin and the biochemical pathways involved in its production; (3) the neuroecology of the ...


The Drrab System Of Streptomyces Peucetius Is A Multi-Drug Transporter Of Broad Substrate Specificity, Wen Li, Madhu Sharma, Parjit Kaur Mar 2014

The Drrab System Of Streptomyces Peucetius Is A Multi-Drug Transporter Of Broad Substrate Specificity, Wen Li, Madhu Sharma, Parjit Kaur

Biology Faculty Publications

The soil bacterium Streptomyces peucetius produces two widely used anticancer antibiotics doxorubicin and daunorubicin. Present within the biosynthesis gene cluster in S. peucetius is the drrAB operon which codes for a dedicated ABC-type transporter for the export of these two closely related antibiotics. Because of its dedicated nature, the DrrAB system is believed to belong to the category of single-drug transporters. However, whether it also contains specificity for other known substrates of multidrug transporters has never been tested. In this study, we demonstrate under both in vivo and in vitro conditions that the DrrAB system can transport not only doxorubicin ...


Intestinal Cgi-58 Deficiency Reduces Postprandial Lipid Absorption, Ping Xie, Feng Guo, Yinyan Ma, Hongling Xhu, Freddy Wang, Bingzhong Xue, Hang Shi, Jian Yang, Liqing Yu Mar 2014

Intestinal Cgi-58 Deficiency Reduces Postprandial Lipid Absorption, Ping Xie, Feng Guo, Yinyan Ma, Hongling Xhu, Freddy Wang, Bingzhong Xue, Hang Shi, Jian Yang, Liqing Yu

Biology Faculty Publications

Comparative Gene Identification-58 (CGI-58), a lipid droplet (LD)-associated protein, promotes intracellular triglyceride (TG) hydrolysis in vitro. Mutations in human CGI-58 cause TG accumulation in numerous tissues including intestine. Enterocytes are thought not to store TG-rich LDs, but a fatty meal does induce temporary cytosolic accumulation of LDs. Accumulated LDs are eventually cleared out, implying existence of TG hydrolytic machinery in enterocytes. However, identities of proteins responsible for LD-TG hydrolysis remain unknown. Here we report that intestine-specific inactivation of CGI-58 in mice significantly reduces postprandial plasma TG concentrations and intestinal TG hydrolase activity, which is associated with a 4-fold increase ...


Colonic Mirna Expression/Secretion, Regulated By Intestinal Epithelial Pept1, Plays An Important Role In Cell-To-Cell Communication During Colitis, Saravanan Ayyadurai, Moiz A. Charania, Bo Xiao, Emilie Viennois, Yuchen Zhang, Didieer Merlin Feb 2014

Colonic Mirna Expression/Secretion, Regulated By Intestinal Epithelial Pept1, Plays An Important Role In Cell-To-Cell Communication During Colitis, Saravanan Ayyadurai, Moiz A. Charania, Bo Xiao, Emilie Viennois, Yuchen Zhang, Didieer Merlin

Biology Faculty Publications

PepT1 is a member of the proton-oligopeptide cotransporter family SLC15, which mediates the transport of di/tripeptides from intestinal lumen into epithelial cells. MicroRNAs (miRNAs), a small noncoding RNAs (21–23 nucleotides), posttranscriptionally regulate gene expression by binding to the 39-untranslated regions (UTRs) of their target mRNAs. Although the role of most miRNAs remains elusive, they have been implicated in vital cellular functions such as intestinal epithelial cells differentiation, proliferation, and apoptosis. In the present study, we investigated the effect of intestinal epithelial PepT1 expression on microRNA (miRNA) expression/secretion in the colons of control mice and in mice with ...


Quantitative Multi-Parametric Evaluation Of Centrosome Declustering Drugs: Centrosome Amplification, Mitotic Phenotype, Cell Cycle And Death, Vaishali Pannu, Ritu Aneja, Angela Ogden, A. Cheng, Pcg Rida, R. Osan, Robert Clewley Jan 2014

Quantitative Multi-Parametric Evaluation Of Centrosome Declustering Drugs: Centrosome Amplification, Mitotic Phenotype, Cell Cycle And Death, Vaishali Pannu, Ritu Aneja, Angela Ogden, A. Cheng, Pcg Rida, R. Osan, Robert Clewley

Biology Faculty Publications

Unlike normal cells, cancer cells contain amplified centrosomes and rely on centrosome clustering mechanisms to form a pseudobipolar spindle that circumvents potentially fatal spindle multipolarity (MP). Centrosome clustering also promotes lowgrade chromosome missegregation, which can drive malignant transformation and tumor progression. Putative ‘centrosome declustering drugs’ represent a cancer cell-specific class of chemotherapeutics that produces a common phenotype of centrosome declustering and spindle MP. However, differences between individual agents in terms of efficacy and phenotypic nuances remain unexplored. Herein, we have developed a conceptual framework for the quantitative evaluation of centrosome declustering drugs by investigating their impact on centrosomes, clustering, spindle ...


Centrosome-Declustering Drugs Mediate A Two-Pronged Attack On Interphase And Mitosis In Supercentrosomal Cancer Cells, Vaishali Pannu, Pcg Rida, Betul Celik, Ravi Turaga, Angela Ogden, Guilherme Cantuaria, Jay Gopalakrishnan, Ritu Aneja Jan 2014

Centrosome-Declustering Drugs Mediate A Two-Pronged Attack On Interphase And Mitosis In Supercentrosomal Cancer Cells, Vaishali Pannu, Pcg Rida, Betul Celik, Ravi Turaga, Angela Ogden, Guilherme Cantuaria, Jay Gopalakrishnan, Ritu Aneja

Biology Faculty Publications

Classical anti-mitotic drugs have failed to translate their preclinical efficacy into clinical response in human trials. Their clinical failure has challenged the notion that tumor cells divide frequently at rates comparable to those of cancer cells in vitro and in xenograft models. Given the preponderance of interphase cells in clinical tumors, we asked whether targeting amplified centrosomes, which cancer cells carefully preserve in a tightly clustered conformation throughout interphase, presents a superior chemotherapeutic strategy that sabotages interphase-specific cellular activities, such as migration. Herein we have utilized supercentrosomal N1E-115 murine neuroblastoma cells as a test-bed to study interphase centrosome declustering induced ...


Macrophage Cgi-58 Deficiency Activates Ros-Inflammasome Pathway To Promote Insulin Resistance In Mice, Hongming Miao, Juanjuan Ou, Yinyan Ma, Feng Guo, Zhenggang Yang, Melvin Wiggins, Chaohong Liu, Wenxia Song, Xianlin Han, Miao Wang, Qiang Cao, Bik-Ho Florence Chung, Dan Yang, Houjie Liang, Bingzhong Xue, Hang Shi, Lixia Gan, Liqing Yu Jan 2014

Macrophage Cgi-58 Deficiency Activates Ros-Inflammasome Pathway To Promote Insulin Resistance In Mice, Hongming Miao, Juanjuan Ou, Yinyan Ma, Feng Guo, Zhenggang Yang, Melvin Wiggins, Chaohong Liu, Wenxia Song, Xianlin Han, Miao Wang, Qiang Cao, Bik-Ho Florence Chung, Dan Yang, Houjie Liang, Bingzhong Xue, Hang Shi, Lixia Gan, Liqing Yu

Biology Faculty Publications

No abstract provided.


Loss Of Abhd5 Promotes Colorectal Tumor Development And Progression By Inducing Aerobic Glycolysis And Epithelial-Mesenchymal Transition, Juanjuan Ou, Hongming Miao, Yinyan Ma, Feng Guo, Jia Deng, Xing Wei, Jie Zhou, Ganfeng Xie, Hang Shi, Bingzhong Xue, Houjie Liang, Liqing Yu Jan 2014

Loss Of Abhd5 Promotes Colorectal Tumor Development And Progression By Inducing Aerobic Glycolysis And Epithelial-Mesenchymal Transition, Juanjuan Ou, Hongming Miao, Yinyan Ma, Feng Guo, Jia Deng, Xing Wei, Jie Zhou, Ganfeng Xie, Hang Shi, Bingzhong Xue, Houjie Liang, Liqing Yu

Biology Faculty Publications

How cancer cells shift metabolism to aerobic glycolysis is largely unknown. Here, we show that deficiency of a/b-hydrolase domain-containing 5 (Abhd5), an intracellular lipolytic activator that is also known as comparative gene identification 58 (CGI-58), promotes this metabolic shift and enhances malignancies of colorectal carcinomas (CRCs). Silencing of Abhd5 in normal fibroblasts induces malignant transformation. Intestine-specific knockout of Abhd5 in ApcMin/+ mice robustly increases tumorigenesis and malignant transformation of adenomatous polyps. In colon cancer cells, Abhd5 deficiency induces epithelial-mesenchymal transition by suppressing the AMPKa-p53 pathway, which is attributable to increased aerobic glycolysis. In human CRCs, Abhd5 expression falls substantially ...


New Vaccines Against Influenza Virus, Young-Tae Lee, Ki-Hye Kim, Eun-Ju Ko, Yu-Na Lee, Min-Chul Kim, Young-Man Kwon, Yinghua Tang, Min-Kyoung Cho, Youn-Jeong Lee, Sang-Moon Kang Jan 2014

New Vaccines Against Influenza Virus, Young-Tae Lee, Ki-Hye Kim, Eun-Ju Ko, Yu-Na Lee, Min-Chul Kim, Young-Man Kwon, Yinghua Tang, Min-Kyoung Cho, Youn-Jeong Lee, Sang-Moon Kang

Biology Faculty Publications

Vaccination is one of the most effective and cost-benefit interventions that prevent the mortality and reduce morbidity from infectious pathogens. However, the licensed influenza vaccine induces strain-specific immunity and must be updated annually based on predicted strains that will circulate in the upcoming season. Influenza virus still causes significant health problems worldwide due to the low vaccine efficacy from unexpected outbreaks of next epidemic strains or the emergence of pandemic viruses. Current influenza vaccines are based on immunity to the hemagglutinin antigen that is highly variable among different influenza viruses circulating in humans and animals. Several scientific advances have been ...


The Crimson Conundrum: Heme Toxicity And Tolerance In Gas, Ankita J. Sachla, Yoann Le Breton, Fahmina Akhter, Kevin S. Mciver, Zehava Eichenbaum, Ankita J. Sachla Jan 2014

The Crimson Conundrum: Heme Toxicity And Tolerance In Gas, Ankita J. Sachla, Yoann Le Breton, Fahmina Akhter, Kevin S. Mciver, Zehava Eichenbaum, Ankita J. Sachla

Biology Faculty Publications

The massive erythrocyte lysis caused by the Group A Streptococcus (GAS) suggests that the β-hemolytic pathogen is likely to encounter free heme during the course of infection. In this study, we investigated GAS mechanisms for heme sensing and tolerance. We compared the minimal inhibitory concentration of heme among several isolates and established that excess heme is bacteriostatic and exposure to sub-lethal concentrations of heme resulted in noticeable damage to membrane lipids and proteins. Pre-exposure of the bacteria to 0.1 μM heme shortened the extended lag period that is otherwise observed when naive cells are inoculated into heme-containing medium, implying ...


Dopaminergic Tone Persistently Regulates Voltage-Gated Ion Current Densities Through The D1r-Pka Axis, Rna Polymerase Ii Transcription, Rnai, Mtorc1, And Translation, Wulf-Dieter C. Krenz, Anna R. Parker, Edmund William Rodgers, Deborah J. Baro Jan 2014

Dopaminergic Tone Persistently Regulates Voltage-Gated Ion Current Densities Through The D1r-Pka Axis, Rna Polymerase Ii Transcription, Rnai, Mtorc1, And Translation, Wulf-Dieter C. Krenz, Anna R. Parker, Edmund William Rodgers, Deborah J. Baro

Biology Faculty Publications

Long-term intrinsic and synaptic plasticity must be coordinated to ensure stability and flexibility in neuronal circuits. Coordination might be achieved through shared transduction components. Dopamine (DA) is a well-established participant in many forms of long-term synaptic plasticity. Recent work indicates that DA is also involved in both activity-dependent and -independent forms of long-term intrinsic plasticity. We previously examined DA-enabled long-term intrinsic plasticity in a single identified neuron. The lateral pyloric (LP) neuron is a component of the pyloric network in the crustacean stomatogastric nervous system (STNS). LP expresses type 1 DA receptors (D1Rs). A 1 h bath application of 5 ...


Dopamine Signaling In C. Elegans Is Mediated In Part By Hlh-17-Dependent Regulation Of Extracellular Dopamine Levels, Chaquettea M. Felton, Casonya Matese Johnson Jan 2014

Dopamine Signaling In C. Elegans Is Mediated In Part By Hlh-17-Dependent Regulation Of Extracellular Dopamine Levels, Chaquettea M. Felton, Casonya Matese Johnson

Biology Faculty Publications

In Caenorhabditis elegans, the dopamine transporter DAT-1 regulates synaptic dopamine (DA) signaling by controlling extracellular DA levels. In dat-1(ok157) animals, DA is not taken back up presynaptically but instead reaches extrasynpatic sites, where it activates the dopamine receptor DOP-3 on choligeneric motor neurons and causes animals to become paralyzed in water. This phenotype is called swimming-induced paralysis (SWIP) and is dependent on dat-1 and dop-3. Upstream regulators of dat-1 and dop-3 have yet to be described in C. elegans. In our previous studies, we defined a role for HLH-17 during dopamine response through its regulation of the dopamine receptors ...


Structures Of Darunavir-Resistant Hiv-1 Protease Mutant Reveal Atypical Binding Of Darunavir To Wide Open Flaps, Ying Zhang, Yu-Chung E. Chang, John M. Louis, Yuan Fang Wang, Robert W. Harrison, Irene Weber Jan 2014

Structures Of Darunavir-Resistant Hiv-1 Protease Mutant Reveal Atypical Binding Of Darunavir To Wide Open Flaps, Ying Zhang, Yu-Chung E. Chang, John M. Louis, Yuan Fang Wang, Robert W. Harrison, Irene Weber

Biology Faculty Publications

The molecular basis for high resistance to clinical inhibitors of HIV-1 protease (PR) was examined for the variant designated PRP51 that was selected for resistance to darunavir (DRV). High resolution crystal structures of PRP51 with the active site D25N mutation revealed a ligand-free form and an inhibitor-bound form showing a unique binding site and orientation for DRV. This inactivating mutation is known to increase the dimer dissociation constant and decrease DRV affinity of PR. The PRP51-D25N dimers were in the open conformation with widely separated flaps, as reported for other highly resistant variants. PRP51-D25N dimer bound two DRV molecules and ...


Immunomodulatory Activity Of Red Ginseng Against Influenza A Virus Infection, Jong Seok Lee, Hye Suk Hwang, Eun-Ju Ko, Yu-Na Lee, Young-Man Kwon, Min-Chul Kim, Sang-Moo Kang Jan 2014

Immunomodulatory Activity Of Red Ginseng Against Influenza A Virus Infection, Jong Seok Lee, Hye Suk Hwang, Eun-Ju Ko, Yu-Na Lee, Young-Man Kwon, Min-Chul Kim, Sang-Moo Kang

Biology Faculty Publications

Ginseng herbal medicine has been known to have beneficial effects on improving human health. We investigated whether red ginseng extract (RGE) has preventive effects on influenza A virus infection in vivo and in vitro. RGE was found to improve survival of human lung epithelial cells upon influenza virus infection. Also, RGE treatment reduced the expression of pro-inflammatory genes (IL-6, IL-8) probably in part through interference with the formation of reactive oxygen species by influenza A virus infection. Long-term oral administration of mice with RGE showed multiple immunomodulatory effects such as stimulating antiviral cytokine IFN-γ production after influenza A virus infection ...


Eccentric Contractions Disrupt Fkbp12 Content In Mouse Skeletal Muscle, Cory W. Baumann, Russell George Rogers Iii, Nidhi Gahlot, Chris Ingalls Jan 2014

Eccentric Contractions Disrupt Fkbp12 Content In Mouse Skeletal Muscle, Cory W. Baumann, Russell George Rogers Iii, Nidhi Gahlot, Chris Ingalls

Biology Faculty Publications

Strength deficits associated with eccentric contraction-induced muscle injury stem, in part, from impaired voltage-gated sarcoplasmic reticulum (SR) Ca2+ release. FKBP12 is a 12-kD immunophilin known to bind to the SR Ca2+ release channel (ryanodine receptor, RyR1) and plays an important role in excitation-contraction coupling. To assess the effects of eccentric contractions on FKBP12 content, we measured anterior crural muscle (tibialis anterior [TA], extensor digitorum longus [EDL], extensor hallucis longus muscles) strength and FKBP12 content in pellet and supernatant fractions after centrifugation via immunoblotting from mice before and after a single bout of either 150 eccentric or concentric contractions. There were ...