Digital Commons Network^™

Cardiac Dysfunction After Cancer Treatment, Michael S Ewer, Sandra M Swain, Daniela Cardinale, Anecita Fadol, Thomas M Suter

The Texas Heart Institute Journal

Onco-cardiology is an evolving discipline that requires the consideration of cardiotoxicity in preclinical, clinical,and therapeutic aspects of protocol development,treatment, and surveillance of patients who have undergone interventions using cardiotoxic agents. Only then can we foster new ways to maximize survival while keeping cardiac damage within acceptable limits. It is to this end that our working together has brought us to our present understanding. In the future, we may expect onco-cardiology to play an even greater role in the care of cancer patients.

A Dosing Study Of Bone Marrow Mononuclear Cells For Transendocardial Injection In A Pig Model Of Chronic Ischemic Heart Disease, Guilherme V Silva, Marlos R Fernandes, Cristiano O Cardoso, Ricardo R Sanz, Edie M Oliveira, Pilar Jimenez-Quevedo, Javier Lopez, Franca S Angeli, Yi Zheng, James T Willerson, Emerson C Perin

The Texas Heart Institute Journal

We studied the effect of the dose of bone marrow mononuclear cells, delivered via transendocardial injection, upon capillary density and fibrosis in pigs with chronic ischemic heart disease.

Pigs (n = 16) that had undergone ameroid constrictor placement (left circumflex coronary artery) to induce chronic ischemia were divided equally into 4 groups on the basis of bone marrow mononuclear cell dose: control (saline injection) and 50, 100, or 200 × 106 bone marrow mononuclear cells. Thirty days after ameroid placement, each pig received 13 transendocardial NOGA-guided injections. An implantable loop recorder monitored possible arrhythmias caused by cell transplantation. Thirty days …

Paclitaxel Induces Thrombomodulin Downregulation In Human Aortic Endothelial Cells, Huang-Joe Wang, Te-Ling Lu, Haimei Huang, Huey-Chun Huang

The Texas Heart Institute Journal

Patients with paclitaxel-eluting stents are at risk of developing stent thrombosis upon premature discontinuation of dual antiplatelet therapy. In this study, we set out to clarify whether paclitaxel can modulate thrombomodulin expression in human aortic endothelial cells. Human aortic endothelial cells were stimulated with paclitaxel. Methoxyphenyl tetrazolium inner salt cell viability assay, Western blot analysis, real-time polymerase chain reaction, and immunohistochemical assay were performed. In human aortic endothelial cells, paclitaxel (10(-5) to 10(-9) mol/L) treatment for 13 hours caused significant cytotoxicity at drug concentrations greater than 10(-7) mol/L. Paclitaxel (10(-5) to 10(-9) mol/L) treatment for 5 hours downregulated thrombomodulin expression …

Cd34-Positive Stem Cells In The Treatment Of Heart And Vascular Disease In Human Beings, Alexander R Mackie, Douglas W Losordo

The Texas Heart Institute Journal

Bone marrow-derived CD34(+) cells are a well-characterized population of stem cells that have traditionally been used clinically to reconstitute the hematopoietic system after radiation or chemotherapy. More recently, CD34(+) cells have also been shown to induce therapeutic angiogenesis in animal models of myocardial, peripheral, and cerebral ischemia. The mechanism by which CD34(+) cells promote therapeutic angiogenesis is not completely understood, although evidence supports both direct incorporation of the cells into the expanding vasculature and paracrine secretion of angiogenic growth factors that support the developing microvasculature. Phase I and phase II clinical trials have explored the usefulness of CD34(+) cells in …

Heterogeneity Of Left Ventricular Signal Characteristics In Response To Acute Vagal Stimulation During Ventricular Fibrillation In Dogs, Alireza Nazeri, Macarthur A Elayda, Lubomir Dragnev, Christopher M Frank, Jihong Qu, Valtino X Afonso, Abdi Rasekh, Mohammad Saeed, Jie Cheng, Mossaab Shuraih, Ali Massumi, Mehdi Razavi

The Texas Heart Institute Journal

Studies have shown that long-term vagal stimulation is protective against ventricular fibrillation; however, the effects of acute vagal stimulation during ventricular fibrillation in the normal heart have not been investigated. We examined the effects of acute vagal stimulation on ventricular fibrillation in a canine model. In 4 dogs, we induced 30-second periods of ventricular fibrillation by means of intraventricular pacing. During 2 of the 4 periods of fibrillation that we analyzed, vagal stimulation was delivered through electrodes in the caudal ends of the vagus nerves. Noncontact unipolar electrograms were recorded from 3 ventricular regions: the basal septum, apical septum, and …

Micro-Ultrasonographic Imaging Of Atherosclerotic Progression And Correlation With Inflammatory Markers In Apolipoprotein-E Knockout Mice, Rong-Juan Li, Ya Yang, Yan-Hong Wang, Jin-Jie Xie, Li Song, Zheng Wang, Yao-Zhong Zhang, Yan-Wen Qin, Zhi-An Li, Xiao-Shan Zhang

The Texas Heart Institute Journal

We studied prospectively whether atherosclerotic progression in apolipoprotein-E knockout mice could be noninvasively and accurately measured by use of high-resolution ultrasonographic biomicroscopy. We examined the correlation between the ultrasonographic characterization of ascending aortic atherosclerotic plaque and plasma C-reactive protein, interleukin-1, and interleukin-6 levels in these mice.

In 4 age groups (8, 16, 24, and 32 wk) of 8 male knockout mice each (atherosclerotic groups) and age-matched male C57BL/6 mice (control groups), we used ultrasonographic biomicroscopy to measure maximal plaque thickness or intima-media thickness in the ascending aorta. We compared the findings with corresponding histologic measurements, and we measured plasma C-reactive …

Phosphorylation Meets Nuclear Import: A Review., Jonathan D Nardozzi, Kaylen Lott, Gino Cingolani

Department of Biochemistry and Molecular Biology Faculty Papers

Phosphorylation is the most common and pleiotropic modification in biology, which plays a vital role in regulating and finely tuning a multitude of biological pathways. Transport across the nuclear envelope is also an essential cellular function and is intimately linked to many degeneration processes that lead to disease. It is therefore not surprising that phosphorylation of cargos trafficking between the cytoplasm and nucleus is emerging as an important step to regulate nuclear availability, which directly affects gene expression, cell growth and proliferation. However, the literature on phosphorylation of nucleocytoplasmic trafficking cargos is often confusing. Phosphorylation, and its mirror process dephosphorylation, …

Golgi Cells Operate As State-Specific Temporal Filters At The Input Stage Of The Cerebellar Cortex, Shane A. Heine, Stephen M. Highstein, Pablo M. Blazquez

Open Access Publications

Cerebellar processing of incoming information begins at the synapse between mossy fibers and granule cells, a synapse that is strongly controlled through Golgi cell inhibition. Thus, Golgi cells are uniquely positioned to control the flow of information into the cerebellar cortex and understanding their responses during behavior is essential to understanding cerebellar function. Here we show, for the first time, that Golgi cells express a unique oculomotor-related signal that can be used to provide state- and time-specific filtering of granule cell activity. We used newly established criteria to identify the unique electrophysiological signature of Golgi cells and recorded these neurons …

Midazolam Inhibits Hippocampal Long-Term Potentiation And Learning Through Dual Central And Peripheral Benzodiazepine Receptor Activation And Neurosteroidogenesis, Kazuhiro Tokuda, Kazuko A. O'Dell, Yukitoshi Izumi, Charles F. Zorumski

Open Access Publications

Benzodiazepines (BDZs) enhance GABA(A) receptor inhibition by direct actions on central BDZ receptors (CBRs). Although some BDZs also bind mitochondrial receptors [translocator protein (18 kDa) (TSPO)] and promote the synthesis of GABA-enhancing neurosteroids, the role of neurosteroids in the clinical effects of BDZs is unknown. In rat hippocampal slices, we compared midazolam, an anesthetic BDZ, with clonazepam, an anticonvulsant/anxiolytic BDZ that activates CBRs selectively. Midazolam, but not clonazepam, increased neurosteroid levels in CA1 pyramidal neurons without changing TSPO immunostaining. Midazolam, but not clonazepam, also augmented a form of spike inhibition after stimulation adjacent to the pyramidal cell layer and inhibited …

Expression Of Functional Bacterial Undecaprenyl Pyrophosphate Synthase In The Yeast Rer2{Delta} Mutant And Cho Cells., Jeffrey S. Rush, Sergey Matveev, Ziqiang Guan, Christian R H Raetz, C J Waechter

Molecular and Cellular Biochemistry Faculty Publications

During evolution the average chain length of polyisoprenoid glycosyl carrier lipids increased from C55 (prokaryotes) to C75 (yeast) to C95 (mammalian cells). In this study, the ability of the E. coli enzyme, undecaprenyl pyrophosphate synthase (UPPS), to complement the loss of the yeast cis-isoprenyltransferase in the rer2Δ mutant was tested to determine if (55)dolichyl phosphate (Dol-P) could functionally substitute in the protein N-glycosylation pathway for (75)Dol-P, the normal isoprenologue synthesized in S. cerevisiae. First, expression of UPPS in the yeast mutant was found to complement the growth and the hypoglycosylation of carboxypeptidase Y defects suggesting that the (55)polyprenyl-P-P intermediate was …

C-Jun Inhibits Mammary Apoptosis In Vivo., Sanjay Katiyar, Mathew C Casimiro, Luis Dettin, Xiaoming Ju, Erwin F Wagner, Hirokazu Tanaka, Richard Pestell

Department of Cancer Biology Faculty Papers

c-jun, which is overexpressed in a number of human cancers encodes a critical component of the AP-1 complex. c-jun has been shown to either induce or inhibit cellular apoptosis. Germ line deletion of both c-jun alleles is embryonically lethal. To determine the role of the endogenous c-jun gene in apoptosis, we performed mammary epithelial cell-targeted somatic deletion using floxed c-jun (c-jun(f/f)) conditional knockout mice. Laser capture microdissection demonstrated endogenous c-jun inhibits expression of apoptosis inducing genes and reactive oxygen species (ROS)-reducing genes (MnSOD, catalase). ROS have been implicated in apoptosis and undergo enzymatic elimination via MnSOD and CuZnSOD with further …

Acetate Causes Alcohol Hangover Headache In Rats., Christina R Maxwell, Rebecca Jay Spangenberg, Jan B Hoek, Stephen D Silberstein, Michael L Oshinsky

Department of Neurology Faculty Papers

BACKGROUND: The mechanism of veisalgia cephalgia or hangover headache is unknown. Despite a lack of mechanistic studies, there are a number of theories positing congeners, dehydration, or the ethanol metabolite acetaldehyde as causes of hangover headache.

METHODS: We used a chronic headache model to examine how pure ethanol produces increased sensitivity for nociceptive behaviors in normally hydrated rats.

RESULTS: Ethanol initially decreased sensitivity to mechanical stimuli on the face (analgesia), followed 4 to 6 hours later by inflammatory pain. Inhibiting alcohol dehydrogenase extended the analgesia whereas inhibiting aldehyde dehydrogenase decreased analgesia. Neither treatment had nociceptive effects. Direct administration of acetate …

The Therapeutic Effects Of Working With Dartmoor Ponies: A Pathfinding Project, Dawn Chaplin

The Plymouth Student Scientist

The area of Animal Assisted Therapy, and in particular therapy with Equines, was investigated to assess whether this sort of therapy could contribute to Social and Emotional Aspects of Learning (SEAL). It was proposed that quantitative and qualitative measures would suggest an increase in social and emotional functioning following an Equine Facilitated Learning (EFL) intervention. Three ‘at-risk’ adolescent males were nominated by teaching staff to participate in a quasi-experimental research design, whereby measures were taken but no variables manipulated. Quantitative data provided weak support for the hypothesis although qualitative data suggested an improvement in functioning followed by a decline in …

Biological Rationale For The Use Of Dna Methyltransferase Inhibitors As New Strategy For Modulation Of Tumor Response To Chemotherapy And Radiation., Giovanni L Gravina, Claudio Festuccia, Francesco Marampon, Vladimir M Popov, Richard G Pestell, Bianca M Zani, Vincenzo Tombolini

Kimmel Cancer Center Faculty Papers

Epigenetic modifications play a key role in the patho-physiology of many tumors and the current use of agents targeting epigenetic changes has become a topic of intense interest in cancer research. DNA methyltransferase (DNMT) inhibitors represent a promising class of epigenetic modulators. Research performed yielded promising anti-tumorigenic activity for these agents in vitro and in vivo against a variety of hematologic and solid tumors. These epigenetic modulators cause cell cycle and growth arrest, differentiation and apoptosis. Rationale for combining these agents with cytotoxic therapy or radiation is straightforward since the use of DNMT inhibitor offers greatly improved access for cytotoxic …

Calcium Regulates Vesicle Replenishment At The Cone Ribbon Synapse., Norbert Babai, Theodore M. Bartoletti, Wallace B. Thoreson

Journal Articles: Ophthalmology

Cones release glutamate-filled vesicles continuously in darkness, and changing illumination modulates this release. Because sustained release in darkness is governed by vesicle replenishment rates, we analyzed how cone membrane potential regulates replenishment. Synaptic release from cones was measured by recording postsynaptic currents in Ambystoma tigrinum horizontal or OFF bipolar cells evoked by depolarization of simultaneously voltage-clamped cones. We measured replenishment after attaining a steady state between vesicle release and replenishment using trains of test pulses. Increasing Ca(2+) currents (I(Ca)) by changing the test step from -30 to -10 mV increased replenishment. Lengthening -30 mV test pulses to match the Ca(2+) …

Mouse Cd8alpha+ Dcs And Human Bdca3+ Dcs Are Major Producers Of Ifn-Lambda In Response To Poly Ic., Henning Lauterbach, Barbara Bathke, Stefanie Gilles, Claudia Traidl-Hoffmann, Christian A. Luber, György Fejer, Marina A. Freudenberg, Gayle M. Davey, David Vremec, Axel Kallies, Li Wu, Ken Shortman, Paul Chaplin, Mark Suter, Meredith O'Keeffe, Hubertus Hochrein

School of Biomedical Sciences

Polyinosinic:polycytidylic acid (poly IC), a double-stranded RNA, is an effective adjuvant in vivo. IFN-λs (also termed IL-28/29) are potent immunomodulatory and antiviral cytokines. We demonstrate that poly IC injection in vivo induces large amounts of IFN-λ, which depended on hematopoietic cells and the presence of TLR3 (Toll-like receptor 3), IRF3 (IFN regulatory factor 3), IRF7, IFN-I receptor, Fms-related tyrosine kinase 3 ligand (FL), and IRF8 but not on MyD88 (myeloid differentiation factor 88), Rig-like helicases, or lymphocytes. Upon poly IC injection in vivo, the IFN-λ production by splenocytes segregated with cells phenotypically resembling CD8α(+) conventional dendritic cells (DCs [cDCs]). In …

Biparental Mucus Feeding: A Unique Example Of Parental Care In An Amazonian Cichlid., Jonathan Buckley, Richard J. Maunder, Andrew Foey, Janet Pearce, Adalberto L. Val, Katherine A. Sloman

School of Biomedical Sciences

Vertebrates display a wide variety of parental care behaviours, including the guarding of offspring pre and post nutritional independence as well as the direct provision of nutrients during the early development period. The Amazonian cichlid Symphysodon spp. (discus fish) is unusual among fish species, in that both parents provide offspring with mucus secretions to feed from after hatching. This extensive provision of care, which can last up to a month, imposes a physiological demand on both parents and gives rise to conflict between the parent and offspring. Here, we investigated the relationship between parents and offspring during a breeding cycle, …

Carhsp1 Is Required For Effective Tumor Necrosis Factor Alpha Mrna Stabilization And Localizes To Processing Bodies And Exosomes, Jason R. Pfeiffer, Bethany L. Mcavoy, Ryan E. Fecteau, Kristen M. Deleault, Seth A. Brooks

Dartmouth Scholarship

Tumor necrosis factor alpha (TNF-α) is a critical mediator of inflammation, and its production is tightly regulated, with control points operating at nearly every step of its biosynthesis. We sought to identify uncharacterized TNF-α 3' untranslated region (3'UTR)-interacting proteins utilizing a novel screen, termed the RNA capture assay. We identified CARHSP1, a cold-shock domain-containing protein. Knockdown of CARHSP1 inhibits TNF-α protein production in lipopolysaccharide (LPS)-stimulated cells and reduces the level of TNF-α mRNA in both resting and LPS-stimulated cells. mRNA stability assays demonstrate that CARHSP1 knockdown decreases TNF-α mRNA stability from a half-life (t(1/2)) of 49 min to a t(1/2) …

T-Lymphocyte Responses To Intestinally Absorbed Antigens Can Contribute To Adipose Tissue Inflammation And Glucose Intolerance During High Fat Feeding, Yuehui Wang, Jianing Li, Lihua Tang, Yu Wang, Richard Charnigo, Willem De Villiers, Erik Eckhardt

Internal Medicine Faculty Publications

BACKGROUND: Obesity is associated with inflammation of visceral adipose tissues, which increases the risk for insulin resistance. Animal models suggest that T-lymphocyte infiltration is an important early step, although it is unclear why these cells are attracted. We have recently demonstrated that dietary triglycerides, major components of high fat diets, promote intestinal absorption of a protein antigen (ovalbumin, "OVA"). The antigen was partly transported on chylomicrons, which are prominently cleared in adipose tissues. We hypothesized that intestinally absorbed gut antigens may cause T-lymphocyte associated inflammation in adipose tissue.

METHODOLOGY/PRINCIPAL FINDINGS: Triglyceride absorption promoted intestinal absorption of OVA into adipose tissue, …

Leishmania Major Survival In Selective Phlebotomus Papatasi Sand Fly Vector Requires A Specific Scg-Encoded Lipophosphoglycan Galactosylation Pattern, Deborah E. Dobson, Shaden Kamhawi, Phillip Lawyer, Salvatore J. Turco, Stephen M. Beverley, David L. Sacks

Molecular and Cellular Biochemistry Faculty Publications

Phlebotomine sand flies that transmit the protozoan parasite Leishmania differ greatly in their ability to support different parasite species or strains in the laboratory: while some show considerable selectivity, others are more permissive. In "selective" sand flies, Leishmania binding and survival in the fly midgut typically depends upon the abundant promastigote surface adhesin lipophosphoglycan (LPG), which exhibits species- and strain-specific modifications of the dominant phosphoglycan (PG) repeat units. For the "selective" fly Phlebotomus papatasi PpapJ, side chain galactosyl-modifications (scGal) of PG repeats play key roles in parasite binding. We probed the specificity and properties of this scGal-LPG PAMP (Pathogen Associated …

Intestinal Epithelial Serum Amyloid A Modulates Bacterial Growth In Vitro And Pro-Inflammatory Responses In Mouse Experimental Colitis, Erik R.M. Eckhardt, Jassir Witta, Jian Zhong, Razvan Arsenescu, Violeta Arsenescu, Yu Wang, Sarbani Ghoshal, Marcielle C. De Beer, Frederick C. De Beer, Willem J.S. De Villiers

Internal Medicine Faculty Publications

BACKGROUND: Serum Amyloid A (SAA) is a major acute phase protein of unknown function. SAA is mostly expressed in the liver, but also in other tissues including the intestinal epithelium. SAA reportedly has anti-bacterial effects, and because inflammatory bowel diseases (IBD) result from a breakdown in homeostatic interactions between intestinal epithelia and bacteria, we hypothesized that SAA is protective during experimental colitis.

METHODS: Intestinal SAA expression was measured in mouse and human samples. Dextran sodium sulfate (DSS) colitis was induced in SAA 1/2 double knockout (DKO) mice and in wildtype controls. Anti-bacterial effects of SAA1/2 were tested in intestinal epithelial …

Micrornas Reveal The Interrelationships Of Hagfish, Lampreys, And Gnathostomes And The Nature Of The Ancestral Vertebrate, Alysha M. Heimberg, Richard Cowper-Sal{Middle Dot}Lari, Marie Semon, Philip C. J. Donoghue, Kevin J. Peterson

Dartmouth Scholarship

Hagfish and lampreys are the only living representatives of the jawless vertebrates (agnathans), and compared with jawed vertebrates (gnathostomes), they provide insight into the embryology, genomics, and body plan of the ancestral vertebrate. However, this insight has been obscured by controversy over their interrelationships. Morphological cladistic analyses have identified lampreys and gnathostomes as closest relatives, whereas molecular phylogenetic studies recover a monophyletic Cyclostomata (hagfish and lampreys as closest relatives). Here, we show through deep sequencing of small RNA libraries, coupled with genomic surveys, that Cyclostomata is monophyletic: hagfish and lampreys share 4 unique microRNA families, 15 unique paralogues of more …

The Endogenous Soluble Vegf Receptor-2 Isoform Suppresses Lymph Node Metastasis In A Mouse Immunocompetent Mammary Cancer Model, Masa-Aki Shibata, Jayakrishna Ambati, Eiko Shibata, Romulo J. C. Albuquerque, Junji Morimoto, Yuko Ito, Yoshinori Otsuki

Ophthalmology and Visual Science Faculty Publications

BACKGROUND: Cancer metastasis contributes significantly to cancer mortality and is facilitated by lymphangiogenesis and angiogenesis. A new splicing variant, endogenous soluble vascular endothelial growth factor receptor-2 (esVEGFR-2) that we recently identified is an endogenous selective inhibitor of lymphangiogenesis. To evaluate the antimetastatic potential of esVEGFR-2, gene therapy with vector expressing esVEGFR-2 (pesVEGFR-2) or endostatin (pEndo) as a positive control was conducted on murine metastatic mammary cancer.

METHODS: Syngeneic inoculated metastatic mammary cancers received direct intratumoral injection of pesVEGFR-2, pEndo or pVec as control, once a week for six weeks. In vivo gene electrotransfer was performed on the tumors after each …

Chronic Spontaneous Activity Generated In The Somata Of Primary Nociceptors Is Associated With Pain-Related Behavior After Spinal Cord Injury, Supinder S Bedi, Qing Yang, Robyn J Crook, Junhui Du, Zizhen Wu, Harvey M Fishman, Raymond J Grill, Susan M Carlton, Edgar T Walters

Faculty, Staff and Student Publications

Mechanisms underlying chronic pain that develops after spinal cord injury (SCI) are incompletely understood. Most research on SCI pain mechanisms has focused on neuronal alterations within pain pathways at spinal and supraspinal levels associated with inflammation and glial activation. These events might also impact central processes of primary sensory neurons, triggering in nociceptors a hyperexcitable state and spontaneous activity (SA) that drive behavioral hypersensitivity and pain. SCI can sensitize peripheral fibers of nociceptors and promote peripheral SA, but whether these effects are driven by extrinsic alterations in surrounding tissue or are intrinsic to the nociceptor, and whether similar SA occurs …

The Eagleville Times,Volume 8, Issue 11, Debbie Ryan

Eagleville Times

No abstract provided.

Ms4a4b, A Cd20 Homologue In T Cells, Inhibits T Cell Propagation By Modulation Of Cell Cycle., Hui Xu, Yaping Yan, Mark S Williams, Gregory B Carey, Jingxian Yang, Hongmei Li, Guang-Xian Zhang, Abdolmohamad Rostami

Department of Neurology Faculty Papers

MS4a4B, a CD20 homologue in T cells, is a novel member of the MS4A gene family in mice. The MS4A family includes CD20, FcεRIβ, HTm4 and at least 26 novel members that are characterized by their structural features: with four membrane-spanning domains, two extracellular domains and two cytoplasmic regions. CD20, FcεRIβ and HTm4 have been found to function in B cells, mast cells and hematopoietic cells respectively. However, little is known about the function of MS4a4B in T cell regulation. We demonstrate here that MS4a4B negatively regulates mouse T cell proliferation. MS4a4B is highly expressed in primary T cells, natural …

Endothelial Cell Capture Of Heparin-Binding Growth Factors Under Flow, Bing Zhao, Changjiang Zhang, Kimberly Forsten-Williams, Jun Zhang, Michael Fannon

Ophthalmology and Visual Science Faculty Publications

Circulation is an important delivery method for both natural and synthetic molecules, but microenvironment interactions, regulated by endothelial cells and critical to the molecule's fate, are difficult to interpret using traditional approaches. In this work, we analyzed and predicted growth factor capture under flow using computer modeling and a three-dimensional experimental approach that includes pertinent circulation characteristics such as pulsatile flow, competing binding interactions, and limited bioavailability. An understanding of the controlling features of this process was desired. The experimental module consisted of a bioreactor with synthetic endothelial-lined hollow fibers under flow. The physical design of the system was incorporated …

Plant Phenolics: Extraction, Analysis And Their Antioxidant And Anticancer Properties, Jin Dai, Russell J. Mumper

Pharmaceutical Sciences Faculty Publications

Phenolics are broadly distributed in the plant kingdom and are the most abundant secondary metabolites of plants. Plant polyphenols have drawn increasing attention due to their potent antioxidant properties and their marked effects in the prevention of various oxidative stress associated diseases such as cancer. In the last few years, the identification and development of phenolic compounds or extracts from different plants has become a major area of health- and medical-related research. This review provides an updated and comprehensive overview on phenolic extraction, purification, analysis and quantification as well as their antioxidant properties. Furthermore, the anticancer effects of phenolics in-vitro …

Simvastatin Enhances Immune Responses To Aβ Vaccination And Attenuates Vaccination-Induced Behavioral Alterations, Jinghong Kou, Hong-Duck Kim, Jingji Jin, Dongfeng Cao, Ling Li, Robert Lalonde, Ken-Ichiro Fukuchi

NYMC Faculty Publications

Statins are widely used to lower cholesterol levels by inhibiting cholesterol biosynthesis. Some evidence has indicated that statins might have therapeutic and preventive benefits for Alzheimer's disease (AD). We and others also have shown the beneficial effect of statin treatment in reversing learning and memory deficits in animal models of AD. However, data from clinical trials are inconclusive. We previously documented that the adenovirus vector encoding 11 tandem repeats of Aβ1-6 fused to the receptor-binding domain (Ia) of Pseudomonas exotoxin A, AdPEDI-(Aβ1-6)(11), is effective in inducing an immune response against amyloid-β protein (Aβ) and reducing brain Aβ load in Alzheimer's …

Membrane Anchoring Subunits Specify Selective Regulation Of Rgs9·Gbeta5 Gap Complex In Photoreceptor Neurons, Yan Cao, Alexander V. Kolesnikov, Ikuo Masuho, Vladimir J. Kefalov, Kirill A. Martemyanov

Open Access Publications

The RGS9·Gβ5 complex is the key regulator of neuronal G-protein signaling and shows remarkable selectivity of subunit composition. In retinal photoreceptors, RGS9·Gβ5 is bound to the membrane anchor R9AP and the complex regulates visual signaling. In the basal ganglia neurons, RGS9·Gβ5 is instead associated with a homologous protein, R7BP, and regulates reward circuit. Switching this selective subunit composition of the complex in rod photoreceptors allowed us to study the molecular underpinning of signaling specificity in diverse G-protein pathways. We have found that both membrane anchoring subunits play a conserved role in regulating protein levels of RGS9·Gβ5 and enhancing the ability …