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Dysregulated Hepatic Methionine Metabolism Drives Homocysteine Elevation In Diet-Induced Nonalcoholic Fatty Liver Disease, Tommy Pacana, Sophie Cazanave, Aurora Verdianelli, Viashali Patel, Hae-Ki Min, Faridoddin Mirshahi, Eoin Quinlavin, Arun J. Sanyal

Internal Medicine Publications

Methionine metabolism plays a central role in methylation reactions, production of glutathione and methylarginines, and modulating homocysteine levels. The mechanisms by which these are affected in NAFLD are not fully understood. The aim is to perform a metabolomic, molecular and epigenetic analyses of hepatic methionine metabolism in diet-induced NAFLD. Female 129S1/SvlmJ;C57Bl/6J mice were fed a chow (n = 6) or high-fat high-cholesterol (HFHC) diet (n = 8) for 52 weeks. Metabolomic study, enzymatic expression and DNA methylation analyses were performed. HFHC diet led to weight gain, marked steatosis and extensive fibrosis. In the methionine cycle, hepatic methionine was depleted (30%, …

State Of The Art On The Evidence Base In Cardiac Regenerative Therapy: Overview Of 41 Systematic Reviews, Mariangela Peruzzi, Elena De Falco, Antonio Abbate, Giuseppe Biondi-Zoccai, Isotta Chementi, Marzia Lotrionte, Umberto Benedetto, Ronak Delewi, Antonino G. M. Marullo, Giacomo Frati

Internal Medicine Publications

Objectives. To provide a comprehensive appraisal of the evidence from secondary research on cardiac regenerative therapy. Study Design and Setting. Overview of systematic reviews of controlled clinical trials concerning stem cell administration or mobilization in patients with cardiovascular disease. Results. After a systematic database search, we short-listed 41 reviews (660 patients). Twenty-two (54%) reviews focused on acute myocardial infarction (AMI), 19 (46%) on chronic ischemic heart disease (IHD) or heart failure (HF), 29 (71%) on bone marrow-derived stem-cells (BMSC), and 36 (88%) to randomized trials only. Substantial variability among reviews was found for validity (AMSTAR score: median 9 [minimum …

Intermittent Hypoxia In Childhood: The Harmful Consequences Versus Potential Benefits Of Therapeutic Uses, Tatiana V. Serebrovskaya, Lei Xi

Internal Medicine Publications

Intermittent hypoxia (IH) often occurs in early infancy in both preterm and term infants and especially at 36–44 weeks postmenstrual age. These episodes of IH could result from sleep-disordered breathing or may be temporally unrelated to apnea or bradycardia events. There are numerous reports indicating adverse effects of IH on development, behavior, academic achievement, and cognition in children with sleep apnea syndrome. It remains uncertain about the exact causative relationship between the neurocognitive and behavioral morbidities and IH and/or its associated sleep fragmentation. On the other hand, well-controlled and moderate IH conditioning/training has been used in sick children for treating …

Rational Combinations Of Targeted Agents In Aml, Prithviraj Bose, Steven Grant

Internal Medicine Publications

Despite modest improvements in survival over the last several decades, the treatment of AML continues to present a formidable challenge. Most patients are elderly, and these individuals, as well as those with secondary, therapy-related, or relapsed/refractory AML, are particularly difficult to treat, owing to both aggressive disease biology and the high toxicity of current chemotherapeutic regimens. It has become increasingly apparent in recent years that coordinated interruption of cooperative survival signaling pathways in malignant cells is necessary for optimal therapeutic results. The modest efficacy of monotherapy with both cytotoxic and targeted agents in AML testifies to this. As the complex …

A Comprehensive Assessment Of Environmental Exposures Among 1000 North American Patients With Primary Sclerosing Cholangitis, With And Without Inflammatory Bowel Disease, J. E. Eaton, B. D. Juran, E. J. Atkinson, E. M. Schlicht, X. Xie, M. De Andrade, C. S. Lammert, V. A. Luketic, J. A. Odin, A. A. Koteish, K. V. Kowdley, K. B. Chopra, G. M. Hirschfield, N. P. Chalasani, K. N. Lazaridis

Internal Medicine Publications

Background

The relationships between primary sclerosing cholangitis (PSC) and the environment are largely unknown.

Aims

To validate associations reported in previous studies and to identify novel environmental exposures among PSC patients.

Methods

We performed a multicenter, case–control analysis utilising self-administered questionnaires. Responses between cases (n = 1000) and controls (n = 663) were compared using multivariable logistic regression adjusted for age and gender. The model was further stratified based on inflammatory bowel disease (IBD) status (with IBD n = 741 without IBD n = 259).

Results

Smoking was associated with PSC only when IBD was present (OR, 0.5; …

State Of The Art On The Evidence Base In Cardiac Regenerative Therapy: Overview Of 41 Systematic Reviews, Mariangela Peruzzi, Elena De Falco, Antonio Abbate, Giuseppe Biondi-Zoccai, Isotta Chimenti, Marzia Lotrionte, Umberto Benedetto, Ronak Delewi, Antonino G. M. Marullo, Giacomo Frati

Internal Medicine Publications

Objectives. To provide a comprehensive appraisal of the evidence from secondary research on cardiac regenerative therapy. Study Design and Setting. Overview of systematic reviews of controlled clinical trials concerning stem cell administration or mobilization in patients with cardiovascular disease. Results. After a systematic database search, we short-listed 41 reviews (660 patients). Twenty-two (54%) reviews focused on acute myocardial infarction (AMI), 19 (46%) on chronic ischemic heart disease (IHD) or heart failure (HF), 29 (71%) on bone marrow-derived stem-cells (BMSC), and 36 (88%) to randomized trials only. Substantial variability among reviews was found for validity (AMSTAR score: median …

Inhibition Of Bcl-2 Sensitizes Mitochondrial Permeability Transition Pore (Mptp) Opening In Ischemia-Damaged Mitochondria, Qun Chen, Haishan Xu, Aijun Xu, Thomas Ross, Elizabeth Bowler, Ying Hu, Edward J. Lesnefsky

Internal Medicine Publications

Background

Mitochondria are critical to cardiac injury during reperfusion as a result of damage sustained during ischemia, including the loss of bcl-2. We asked if bcl-2 depletion not only leads to selective permeation of the outer mitochondrial membrane (MOMP) favoring cytochrome crelease and programmed cell death, but also favors opening of the mitochondrial permeability transition pore (MPTP). An increase in MPTP susceptibility would support a role for bcl-2 depletion mediated cell death in the calcium overload setting of early reperfusion via MPTP as well as later in reperfusion via MOMP as myocardial calcium content normalizes.

Methods

Calcium retention capacity …

Co-Administration Of The Mtorc1/Torc2 Inhibitor Ink128 And The Bcl-2/Bcl-Xl Antagonist Abt-737 Kills Human Myeloid Leukemia Cells Through Mcl-1 Down-Regulation And Akt Inactivation, Mohamed Rahmani, Mandy Mayo Aust, Elisa Hawkins, Rebecca E. Parker, Masey Ross, Maciej Kmieciak, Leonid Borisovich Reshko, Kathryn A. Rizzo, Catherine I. Dumur, Andrea Ferreira-Gonzalez, Steven Grant

Internal Medicine Publications

Effects of concurrent inhibition of mTORC1/2 and Bcl-2/Bcl-xL in human acute myeloid leukemia cells were examined. Tetracycline-inducible Bcl-2/Bcl-xL dual knockdown markedly sensitized acute myeloid leukemia cells to the dual TORC1/2 inhibitor INK128 in vitro as well as in vivo. Moreover, INK128 co-administered with the Bcl-2/xL antagonist ABT-737 sharply induced cell death in multiple acute myeloid leukemia cell lines, including TKI-resistant FLT3-ITD mutants and primary acute myeloid leukemia blasts carrying various genetic aberrations e.g., FLT3, IDH2, NPM1, and Kras, while exerting minimal toxicity toward normal hematopoietic CD34+ cells. Combined treatment was particularly active against CD34+/CD38−/CD123+ primitive leukemic progenitor …

Dysregulated Hepatic Methionine Metabolism Drives Homocysteine Elevation In Diet-Induced Nonalcoholic Fatty Liver Disease, Tommy Pacana, Sophie Cazanave, Aurora Verdianelli, Vaishali Patel, Hae-Ki Min, Faridoddin Mirshahi, Eoin Quinlivan, Arun J. Sanyal

Internal Medicine Publications

Methionine metabolism plays a central role in methylation reactions, production of glutathione and methylarginines, and modulating homocysteine levels. The mechanisms by which these are affected in NAFLD are not fully understood. The aim is to perform a metabolomic, molecular and epigenetic analyses of hepatic methionine metabolism in diet-induced NAFLD. Female 129S1/SvlmJ;C57Bl/6J mice were fed a chow (n = 6) or high-fat high-cholesterol (HFHC) diet (n = 8) for 52 weeks. Metabolomic study, enzymatic expression and DNA methylation analyses were performed. HFHC diet led to weight gain, marked steatosis and extensive fibrosis. In the methionine cycle, hepatic methionine was depleted (30%, …

Inhibition Of Bcl-2 Sensitizes Mitochondrial Permeability Transition Pore (Mptp) Opening In Ischemia-Damaged Mitochondria, Qun Chen, Haishan Xu, Aijun Xu, Thomas Ross, Elizabeth Bowler, Ying Hu, Edward J. Lesnefsky

Internal Medicine Publications

Background

Mitochondria are critical to cardiac injury during reperfusion as a result of damage sustained during ischemia, including the loss of bcl-2. We asked if bcl-2 depletion not only leads to selective permeation of the outer mitochondrial membrane (MOMP) favoring cytochrome c release and programmed cell death, but also favors opening of the mitochondrial permeability transition pore (MPTP). An increase in MPTP susceptibility would support a role for bcl-2 depletion mediated cell death in the calcium overload setting of early reperfusion via MPTP as well as later in reperfusion via MOMP as myocardial calcium content normalizes.

Methods

Calcium retention capacity …

Epigenetic Modifications Of The Pgc-1Α Promoter During Exercise Induced Expression In Mice, Timothy L. Lochmann, Ravindar R. Thomas, James P. Bennett, Shirley M. Taylor

Massey Comprehensive Cancer Center Publications

The transcriptional coactivator, PGC-1α, is known for its role in mitochondrial biogenesis. Although originally thought to exist as a single protein isoform, recent studies have identified additional promoters which produce multiple mRNA transcripts. One of these promoters (promoter B), approximately 13.7kb upstream of the canonical PGC-1α promoter (promoter A), yields alternative transcripts present at levels much lower than the canonical PGC-1α mRNA transcript. In skeletal muscle, exercise resulted in a substantial, rapid increase of mRNA of these alternative PGC-1α transcripts. Although the β2-adrenergic receptor was identified as a signaling pathway that activates transcription from PGC-1α promoter B, it is not …

Role Of Interleukin-1 In Radiation-Induced Cardiomyopathy, Eleonora Mezzaroma, Ross B. Mikkelsen, Stefano Toldo, Adolfo G. Mauro, Khushboo Sharma, Carlo Marchetti, Asim Alam, Benjamin W. Van Tassell, David A. Gewirtz, Antonio Abbate

Pharmacotherapy and Outcomes Science Publications

Thoracic X-ray therapy (XRT), used in cancer treatment, is associated with increased risk of heart failure. XRT-mediated injury to the heart induces an inflammatory response leading to cardiomyopathy. The aim of this study was to determine the role of interleukin (IL)-1 in response to XRT injury to the heart and on the cardiomyopathy development in the mouse. Female mice with genetic deletion of the IL-1 receptor type I (IL-1R1 knockout mice [IL-1R1 KO]) and treatment with recombinant human IL-1 receptor antagonist anakinra, 10 mg/kg twice daily for 7 d, were used as independent approaches to determine the role of IL-1. …

Dismira: Prioritization Of Disease Candidates In Mirna-Disease Associations Based On Maximum Weighted Matching Inference Model And Motif-Based Analysis, Joseph J. Nalluri, Bhanu K. Kamapantula, Debmalya Barh, Neha Jain, Antaripa Bhattacharya, Sintia Silva De Almeida, Rommel Thiago Juca Ramos, Artur Silva, Vasco Azevedo, Preetam Ghosh

Computer Science Publications

Background

MicroRNAs (miRNAs) have increasingly been found to regulate diseases at a significant level. The interaction of miRNA and diseases is a complex web of multilevel interactions, given the fact that a miRNA regulates upto 50 or more diseases and miRNAs/diseases work in clusters. The clear patterns of miRNA regulations in a disease are still elusive.

Methods

In this work, we approach the miRNA-disease interactions from a network scientific perspective and devise two approaches - maximum weighted matching model (a graph theoretical algorithm which provides the result by solving an optimization equation of selecting the most prominent set of diseases) …

Maprepeat: An Approach For Effective Assembly Of Repetitive Regions In Prokaryotic Genomes, Diego Cb Mariano, Felipe L. Pereira, Preetam Ghosh, Debmalya Barh, Henrique Cp Figueiredo, Artur Silva, Rommel Tj Ramos, Vasco Ac Azevedo

Computer Science Publications

The newest technologies for DNA sequencing have led to the determination of the primary structure of the genomes of organisms, mainly prokaryotes, with high efficiency and at lower costs. However, the presence of regions with repetitive sequences, in addition to the short reads produced by the Next-Generation Sequencing (NGS) platforms, created a lot of difficulty in reconstructing the original genome in silico. Thus, even today, genome assembly continues to be one of the major challenges in bioinformatics specifically when repetitive sequences are considered. In this paper, we present an approach to assemble repetitive regions in prokaryotic genomes. Our methodology …

Novel Zno Hollow-Nanocarriers Containing Paclitaxel Targeting Folate-Receptors In A Malignant Ph-Microenvironment For Effective Monitoring And Promoting Breast Tumor Regression, Nagaprasad Puvvada, Shashi Rajput, B. N. Prashanth Kumar, Siddik Sarkar, Suraj Konar, Keith R. Brunt, Raj R. Rao, Abhijit Mazumdar, Swadesh K. Das, Ranadhir Basu, Paul B. Fisher, Mahitosh Mandal, Amita Pathak

VCU Health Publications

Low pH in the tumor micromilieu is a recognized pathological feature of cancer. This attribute of cancerous cells has been targeted herein for the controlled release of chemotherapeutics at the tumour site, while sparing healthy tissues. To this end, pH-sensitive, hollow ZnO-nanocarriers loaded with paclitaxel were synthesized and their efficacy studied in breast cancer in vitro and in vivo. The nanocarriers were surface functionalized with folate using click-chemistry to improve targeted uptake by the malignant cells that over-express folate-receptors. The nanocarriers released ~75% of the paclitaxel payload within six hours in acidic pH, which was accompanied by switching of …

Urban Pets As Social Practice: Constructing Pets With A Purpose, Carrie Pope

Middle School Resources

I developed this lesson in my fourteenth year of teaching. I had just transferred to sixth grade general art after primarily teaching pottery classes in a high school for thirteen years. I was at a low income, high poverty school and was having a difficult time engaging my students. I had seen Robert Marbury’s work about ten years earlier and had wanted to do something with it but had never had the opportunity. Recognizing the student's need for play, I first approached this lesson with one class bringing in several garbage bags of stuffed animals my daughter had discarded.

The …

Pde5 Inhibitors Enhance Celecoxib Killing In Multiple Tumor Types, Laurence Booth, Jane L. Roberts, Nichola Cruickshanks, Seyedmehrad Tavallai, Timothy Webb, Peter Samuel, Adam Conley, Brittany Binion, Harold F. Young, Andrew Poklepovic, Sarah Spiegel, Paul Dent

Biochemistry and Molecular Biology Publications

The present studies determined whether clinically relevant phosphodiesterase 5 (PDE5) inhibitors interacted with a clinically relevant NSAID, celecoxib, to kill tumor cells. Celecoxib and PDE5 inhibitors interacted in a greater than additive fashion to kill multiple tumor cell types. Celecoxib and sildenafil killed ex vivo primary human glioma cells as well as their associated activated microglia. Knock down of PDE5 recapitulated the effects of PDE5 inhibitor treatment; the nitric oxide synthase inhibitor L-NAME suppressed drug combination toxicity. The effects of celecoxib were COX2 independent. Over-expression of c-FLIP-s or knock down of CD95/FADD significantly reduced killing by the drug combination. CD95 …

The Signal Transducer And Activator Of Transcription 1 (Stat1) Inhibits Mitochondrial Biogenesis In Liver And Fatty Acid Oxidation In Adipocytes, Jennifer D. Sisler, Magdalena Morgan, Vidisha Raje, Rebecca C. Grande, Marta Derecka, Jeremy Meier, Marc Cantwell, Karol Szczepanek, William J. Korzun, Edward J. Lesnefsky, Thurl E. Harris, Colleen M. Croniger, Andrew C. Larner

Biochemistry and Molecular Biology Publications

The transcription factor STAT1 plays a central role in orchestrating responses to various pathogens by activating the transcription of nuclear-encoded genes that mediate the antiviral, the antigrowth, and immune surveillance effects of interferons and other cytokines. In addition to regulating gene expression, we report that STAT1-/- mice display increased energy expenditure and paradoxically decreased release of triglycerides from white adipose tissue (WAT). Liver mitochondria from STAT1-/- mice show both defects in coupling of the electron transport chain (ETC) and increased numbers of mitochondria. Consistent with elevated numbers of mitochondria, STAT1-/- mice expressed increased amounts of PGC1α, a …

Generation Of Multicellular Tumor Spheroids With Microwell-Based Agarose Scaffolds For Drug Testing, Xue Gong, Chao Lin, Jian Cheng, Jiansheng Su, Hang Zhao, Tianlin Liu, Xuejun Wen, Peng Zhao

Chemical and Life Science Engineering Publications

Three dimensional multicellular aggregate, also referred to as cell spheroid or microtissue, is an indispensable tool for in vitro evaluating antitumor activity and drug efficacy. Compared with classical cellular monolayer, multicellular tumor spheroid (MCTS) offers a more rational platform to predict in vivo drug efficacy and toxicity. Nevertheless, traditional processing methods such as plastic dish culture with nonadhesive surfaces are regularly time-consuming, laborious and difficult to provide uniform-sized spheroids, thus causing poor reproducibility of experimental data and impeding high-throughput drug screening. In order to provide a robust and effective platform for in vitro drug evaluation, we present an agarose scaffold …

Depletion Of The Chromatin Remodeler Chd4 Sensitizes Aml Blasts To Genotoxic Agents And Reduces Tumor Formation, Justin Sperlazza, Mohamed Rahmani, Jason Beckta, Mandy Aust, Elisa Hawkins, Shou Zhen Wang, Sheng Zu Zhu, Shreya Podder, Catherine Dumur, Kellie Archer, Steven Grant, Gordon D. Ginder

Human and Molecular Genetics Publications

Chromodomain helicase DNA-binding protein 4 (CHD4) is an ATPase that alters the phasing of nucleosomes on DNA and has recently been implicated in DNA double-stranded break (DSB) repair. Here, we show that depletion of CHD4 in acute myeloid leukemia (AML) blasts induces a global relaxation of chromatin that renders cells more susceptible to DSB formation, while concurrently impeding their repair. Furthermore, CHD4 depletion renders AML blasts more sensitive both in vitro and in vivo to genotoxic agents used in clinical therapy: daunorubicin (DNR) and cytarabine (ara-C). Sensitization to DNR and ara-C is mediated in part by activation of the ataxia-telangiectasia …

Evaluation Of Methyl-Binding Domain Based Enrichment Approaches Revisited, Karolina A. Aberg, Linying Xie, Robin F. Chan, Min Zhao, Ashutosh K. Pandey, Gaurav Kumar, Shaunna L. Clark, Edwin J. C. G. Van Den Oord

Human and Molecular Genetics Publications

Methyl-binding domain (MBD) enrichment followed by deep sequencing (MBD-seq), is a robust and cost efficient approach for methylome-wide association studies (MWAS). MBD-seq has been demonstrated to be capable of identifying differentially methylated regions, detecting previously reported robust associations and producing findings that replicate with other technologies such as targeted pyrosequencing of bisulfite converted DNA. There are several kits commercially available that can be used for MBD enrichment. Our previous work has involved MethylMiner (Life Technologies, Foster City, CA, USA) that we chose after careful investigation of its properties. However, in a recent evaluation of five commercially available MBD-enrichment kits the …

Tumor-Specific Expression And Detection Of A Cest Reporter Gene, Il Minn, Amnon Bar-Shir, Keerthi Yarlagadda, Jeff W. M. Bulte, Paul B. Fisher, Hao Wang, Assaf A. Gilad, Martin G. Pomper

Human and Molecular Genetics Publications

Purpose

To develop an imaging tool that enables the detection of malignant tissue with enhanced specificity using the exquisite spatial resolution of MRI.

Methods

Two mammalian gene expression vectors were created for the expression of the lysine-rich protein (LRP) under the control of the cytomegalovirus (CMV) promoter and the progression elevated gene-3 promoter (PEG-3 promoter) for constitutive and tumor-specific expression of LRP, respectively. Using those vectors, stable cell lines of rat 9L glioma, 9LCMV-LRP and 9LPEG-LRP, were established and tested for CEST contrast in vitro and in vivo.

Results

9LPEG-LRP cells showed increased CEST contrast compared with 9L cells …

Tumor-Specific Expression And Detection Of A Cest Reporter Gene, Il Minn, Amnon Bar-Shir, Keerthi Yarlagadda, Jeff W. M. Bulte, Paul B. Fisher, Hao Wang, Assaf A. Gilad, Martin G. Pomper

Human and Molecular Genetics Publications

Purpose

To develop an imaging tool that enables the detection of malignant tissue with enhanced specificity using the exquisite spatial resolution of MRI.

Methods

Two mammalian gene expression vectors were created for the expression of the lysine-rich protein (LRP) under the control of the cytomegalovirus (CMV) promoter and the progression elevated gene-3 promoter (PEG-3 promoter) for constitutive and tumor-specific expression of LRP, respectively. Using those vectors, stable cell lines of rat 9L glioma, 9LCMV-LRP and 9LPEG-LRP, were established and tested for CEST contrast in vitro and in vivo.

Results

9LPEG-LRP cells showed increased CEST contrast compared with 9L cells …

Comparison Of Effects Of P53 Null And Gain-Of-Function Mutations On Salivary Tumors In Mmtv-Hras Transgenic Mice, Dadi Jiang, Catherine I. Dumur, H. Davis Massey, Viswanathan Ramakrishnan, Mark A. Subler, Jolene J. Windle

Human and Molecular Genetics Publications

p53 is an important tumor suppressor gene which is mutated in ~50% of all human cancers. Some of these mutants appear to have acquired novel functions beyond merely losing wild-type functions. To investigate these gain-of-function effects in vivo, we generated mice of three different genotypes: MMTV-Hras/p53+/+, MMTV-Hras/p53-/-, and MMTV-Hras/p53R172H/R172H. Salivary tumors from these mice were characterized with regard to age of tumor onset, tumor growth rates, cell cycle distribution, apoptotic levels, tumor histopathology, as well as response to doxorubicin treatment. Microarray analysis was also performed to profile gene expression. The MMTV-Hras/p53-/- and …

Regulation Of Osteoblast Differentiation By Acid-Etched And/Or Grit-Blasted Titanium Substrate Topography Is Enhanced By 1,25(Oh)2d3 In A Sex-Dependent Manner, Rene Olivares-Navarrete, Sharon L. Hyzy, Barbara D. Boyan, Zvi Schwartz

Biomedical Engineering Publications

This study assessed contributions of micron-scale topography on clinically relevant titanium (Ti) to differentiation of osteoprogenitor cells and osteoblasts; the interaction of this effect with 1𝛼,25-dihydroxyvitamin D₃ (1𝛼,25(OH)₂D₃); and if the effects are sex-dependent. Male and female rat bone marrow cells (BMCs) were cultured on acid-etched (A, 𝑅_𝑎 = 0.87 𝜇m), grit-blasted (GB, 𝑅_𝑎 = 3.90 𝜇m), or grit-blasted/acid-etched (SLA, 𝑅_𝑎 = 3.22 𝜇m) Ti. BMCs were sensitive to surface topography and underwent osteoblast differentiation. This was greatest on SLA; acid etching and grit blasting contributed additively. Primary osteoblasts were also sensitive …

Osteogenic Embryoid Body-Derived Material Induces Bone Formation In Vivo, Ken Sutha, Zvi Schwartz, Yun Wang, Sharon Hyzy, Barbara D. Boyan, Todd C. Mcdevitt

Biomedical Engineering Publications

The progressive loss of endogenous regenerative capacity that accompanies mammalian aging has been attributed at least in part to alterations in the extracellular matrix (ECM) composition of adult tissues. Thus, creation of a more regenerative microenvironment, analogous to embryonic morphogenesis, may be achieved via pluripotent embryonic stem cell (ESC) differentiation and derivation of devitalized materials as an alternative to decellularized adult tissues, such as demineralized bone matrix (DBM). Transplantation of devitalized ESC materials represents a novel approach to promote functional tissue regeneration and reduce the inherent batch-to-batch variability of allograft-derived materials. In this study, the osteoinductivity of embryoid body-derived material …

Widely Used Herpes Simplex Virus 1 Icp0 Deletion Mutant Strain Dl1403 And Its Derivative Viruses Do Not Express Glycoprotein C Due To A Secondary Mutation In The Gc Gene, Cristina W. Cunha, Kathryne E. Taylor, Suzanne M. Pritchard, Mark G. Delboy, Tri Komala Sari, Hector C. Aguilar, Karen L. Mossman, Anthony V. Nicola

Microbiology and Immunology Publications

Herpes simplex virus 1 (HSV-1) ICP0 is a multi-functional phosphoprotein expressed with immediate early kinetics. An ICP0 deletion mutant, HSV-1 dl1403, has been widely used to study the roles of ICP0 in the HSV-1 replication cycle including gene expression, latency, entry and assembly. We show that HSV-1 dl1403 virions lack detectable levels of envelope protein gC, and that gC is not synthesized in infected cells. Sequencing of the gC gene from HSV-1dl1403 revealed a single amino acid deletion that results in a frameshift mutation. The HSV-1dl1403 gC gene is predicted to encode a polypeptide …

Turning Over A New Leaf: Cannabinoid And Endocannabinoid Modulation Of Immune Function, Guy A. Cabral, Thomas J. Rogers, Aron H. Lichtman

Microbiology and Immunology Publications

Cannabis is a complex substance that harbors terpenoid-like compounds referred to as phytocannabinoids. The major psychoactive phytocannabinoid found in cannabis ∆9-tetrahydrocannabinol (THC) produces the majority of its pharmacological effects through two cannabinoid receptors, termed CB1 and CB2. The discovery of these receptors as linked functionally to distinct biological effects of THC, and the subsequent development of synthetic cannabinoids, precipitated discovery of the endogenous cannabinoid (or endocannabinoid) system. This system consists of the endogenous lipid ligands N- arachidonoylethanolamine (anandamide; AEA) and 2-arachidonylglycerol (2-AG), their biosynthetic and degradative enzymes, and the CB1 and CB2 receptors that they activate. Endocannabinoids have been …

Widely Used Herpes Simplex Virus 1 Icp0 Deletion Mutant Strain Dl1403 And Its Derivative Viruses Do Not Express Glycoprotein C Due To A Secondary Mutation In The Gc Gene, Cristina W. Cunha, Kathryne E. Taylor, Suzanne M. Pritchard, Mark Delboy, Tri Komala Sari, Hector C. Aguilar, Karen L. Mossman, Anthony V. Nicola

Microbiology and Immunology Publications

Herpes simplex virus 1 (HSV-1) ICP0 is a multi-functional phosphoprotein expressed with immediate early kinetics. An ICP0 deletion mutant, HSV-1 dl1403, has been widely used to study the roles of ICP0 in the HSV-1 replication cycle including gene expression, latency, entry and assembly. We show that HSV-1dl1403 virions lack detectable levels of envelope protein gC, and that gC is not synthesized in infected cells. Sequencing of the gC gene from HSV-1 dl1403 revealed a single amino acid deletion that results in a frameshift mutation. The HSV-1 dl1403 gC gene is predicted to encode a polypeptide …

Epigenetic Modifications Of The Pgc-1Α Promoter During Exercise Induced Expression In Mice, Timothy L. Lochmann, Ravindar R. Thomas, James P. Bennett Jr., Shirley M. Taylor

Microbiology and Immunology Publications

The transcriptional coactivator, PGC-1α, is known for its role in mitochondrial biogenesis. Although originally thought to exist as a single protein isoform, recent studies have identified additional promoters which produce multiple mRNA transcripts. One of these promoters (promoter B), approximately 13.7kb upstream of the canonical PGC-1α promoter (promoter A), yields alternative transcripts present at levels much lower than the canonical PGC-1α mRNA transcript. In skeletal muscle, exercise resulted in a substantial, rapid increase of mRNA of these alternative PGC-1α transcripts. Although the β2-adrenergic receptor was identified as a signaling pathway that activates transcription from PGC-1α promoter B, it is not …