text:
Richard Ho, M.D., M.S.C.I.
Associate Professor of Pediatrics (Pediatric Hematology and Oncology)
Pediatric Hematologist/Oncologist
- Appointments
Physicians: 1-877-936-8422
- Clinical Trials Information
- Clinical Trials: 1-800-811-8480
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- Other Telephone NumbersMonroe Carell Jr. Children's Hospital at Vanderbilt
(615) 936-1000
- FaxesOffice Fax
Clinic Fax
- Addresses
2220 Pierce Avenue
Nashville, TN 37232
Monroe Carell Jr. Children's Hospital at Vanderbilt
2200 Children's Way
Nashville, TN 37232
Vanderbilt University Medical Center
2220 Pierce Avenue
397 Preston Research Building
Nashville, TN 37232-6310
Dr. Ho is a pediatric hematologist/oncologist and physician scientist whose research focuses on the molecular mechanisms by which drug transporters contribute to overall chemotherapy disposition and interindividual response to drug therapy in pediatric oncology. Drug transport proteins have important roles in regulating the absorption, distribution, and excretion of many medications as well as endogenous substances. To this extent, a major focus in his lab centers on the contribution of uptake transporters, in particular the organic anion transporting polypeptide (OATP) family and bile acid uptake transporters, to the disposition of pediatric chemotherapeutic agents. In addition, another area of major focus is cancer pharmacogenetics, the study of the role of inheritance in the individual variation in chemotherapy response. Projects are primarily laboratory based with translational promise and rely on background knowledge in the fields of molecular biology and clinical pharmacology. His research has been continuously funded by grants (K08, R01) from the National Institute of General Medical Sciences (NIGMS/NIH) since 2007. Dr. Ho is also a co-investigator on a NIH-funded multicenter clinical trial evaluating the pharmacogenetics of vincristine neuropathy in children with acute lymphoblastic leukemia. Dr. Ho's clinical interests are focused on pediatric stem cell transplantation.
- M.D.-Vanderbilt University, Nashville, TN, 1997
- Pediatric Resident-Vanderbilt University Medical Center
- Research Fellow-Pediatric Hematology-Oncology and Clinical Pharmacology; Vanderbilt University
- Clinical Fellow-Pediatric Hematology-Oncology, Vanderbilt University
Research Description
Our research program focuses on the molecular mechanisms by which drug transporters contribute to overall chemotherapy disposition and interindividual response to drug therapy in cancer therapy. Drug transport proteins have important roles in modulating the absorption, distribution, and excretion of many drugs and drug metabolites as well as endogenous substances. They tend to be highly expressed in tissues of importance to drug disposition, including the liver, intestine, kidney and at the blood:brain barrier. To this extent, a major focus in my lab centers on the contribution of specific drug uptake transporters, in particular the organic anion transporting polypeptide (OATP) family and bile acid uptake transporters, to the disposition of pediatric chemotherapeutic agents. In addition, another area of major focus is cancer pharmacogenetics, the study of the role of inheritance in the individual variation in chemotherapy response. Projects are primarily laboratory based with translational promise and rely on background knowledge in the fields of molecular biology and clinical pharmacology. We utilize a number of in vitro techniques to study these transporter proteins, including vaccinia-based expression systems for functional transport studies, drug screening, and drug inhibition studies, protein expression studies utilizing western analysis, immunohistochemistry and immunofluorescent confocal microscopy, and generation of polarized stable cell lines for directional transport studies and comprehensive kinetic analysis. We have also integrated animal models utilizing recently generated knockout mice for various transporter genes into our research program for in vitro:in vivo correlative data in our drug disposition studies.
Moreover, our research has important implications for drug discovery and experimental therapeutics. ADME (absorption, distribution, metabolism and excretion) deficiency is one of the major causes of failure during drug development. In vitro ADME screening of potential lead compounds and drug candidates in the early discovery phase has been employed as a more cost-effective approach to identify compounds that have unfavorable drug-like characteristics. Many compounds with promising pharmacological characteristics never become drugs because they have poor solubility, quickly degrade in biological fluids and tissues or rapidly metabolized in the liver. Utilizing our in vitro screening transport and detailed studies of kinetic analysis, we are able to identify potential drug compounds as substrates for a complement of drug uptake and efflux transporters, which may have important implications not only for drug disposition in vivo, but also for drug toxicity, efficacy and tissue targeting. Furthermore, as many of the transporters we study are known to be polymorphic, we have the ability to assess transporter polymorphisms for differential transport of drugs and/or drug metabolites, which may have significant consequences for determining the interindividual response to anticancer agents.
- Frangoul H, Min E, Wang W, Chandrasekhar R, Calder C, Evans M, Manes B, Bruce K, Brown V, Ho R, Domm J. Incidence and risk factors for hypogammaglobulinemia in pediatric patients following allo-SCT. Bone Marrow Transplant [print-electronic]. 2013 Nov; 48(11): 1456-9. PMID: 23708706, PII: bmt201376, DOI: 10.1038/bmt.2013.76, ISSN: 1476-5365.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/23708706.
- Lavoie Smith EM, Li L, Hutchinson RJ, Ho R, Burnette WB, Wells E, Bridges C, Renbarger J. Measuring vincristine-induced peripheral neuropathy in children with acute lymphoblastic leukemia. Cancer Nurs. 2013 Sep; 36(5): E49-60. PMID: 23842524, PMCID: PMC3951303, DOI: 10.1097/NCC.0b013e318299ad23, ISSN: 1538-9804.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/23842524.
- Vear SI, Stein CM, Ho RH. Warfarin pharmacogenomics in children. Pediatr Blood Cancer [print-electronic]. 2013 Sep; 60(9): 1402-7. PMID: 23682017, PMCID: PMC3786327, DOI: 10.1002/pbc.24592, ISSN: 1545-5017.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/23682017.
- Minson KA, Prasad P, Vear S, Borinstein S, Ho R, Domm J, Frangoul H. T(17;19) in Children with Acute Lymphocytic Leukemia: A Report of 3 Cases and a Review of the Literature. Case Rep Hematol [print-electronic]. 2013; 2013: 563291. PMID: 23346431, PMCID: PMC3549381, DOI: 10.1155/2013/563291, ISSN: 2090-6560.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/23346431.
- McManus MP, Wang L, Calder C, Manes B, Evans M, Bruce K, Ho RH, Domm J, Frangoul H. Comparison of pre-cryopreserved and post-thaw-and-wash-nucleated cell count on major outcomes following unrelated cord blood transplant in children. Pediatr Transplant [print-electronic]. 2012 Aug; 16(5): 438-42. PMID: 22533817, PMCID: PMC3391317, DOI: 10.1111/j.1399-3046.2012.01698.x, ISSN: 1399-3046.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/22533817.
- DeGorter MK, Ho RH, Leake BF, Tirona RG, Kim RB. Interaction of three regiospecific amino acid residues is required for OATP1B1 gain of OATP1B3 substrate specificity. Mol. Pharm [print-electronic]. 2012 Apr 4/2/2012; 9(4): 986-95. PMID: 22352740, PMCID: PMC3319192, DOI: 10.1021/mp200629s, ISSN: 1543-8392.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/22352740.
- Korhonen K, Lovvorn HN, Koyama T, Koehler E, Calder C, Manes B, Evans M, Bruce K, Ho RH, Domm J, Frangoul H. Incidence, risk factors, and outcome of pneumatosis intestinalis in pediatric stem cell transplant recipients. Pediatr Blood Cancer [print-electronic]. 2012 Apr; 58(4): 616-20. PMID: 21721114, DOI: 10.1002/pbc.23242, ISSN: 1545-5017.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/21721114.
- Ho RH, Leake BF, Urquhart BL, Gregor JC, Dawson PA, Kim RB. Functional characterization of genetic variants in the apical sodium-dependent bile acid transporter (ASBT; SLC10A2). J. Gastroenterol. Hepatol. 2011 Dec; 26(12): 1740-8. PMID: 21649730, PMCID: PMC3170668, DOI: 10.1111/j.1440-1746.2011.06805.x, ISSN: 1440-1746.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/21649730.
- Esbenshade AJ, Ho RH, Shintani A, Zhao Z, Smith LA, Friedman DL. Dapsone-induced methemoglobinemia: a dose-related occurrence?. Cancer [print-electronic]. 2011 Aug 8/1/2011; 117(15): 3485-92. PMID: 21246536, PMCID: PMC3138875, DOI: 10.1002/cncr.25904, ISSN: 1097-0142.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/21246536.
- Schwarz UI, Meyer zu Schwabedissen HE, Tirona RG, Suzuki A, Leake BF, Mokrab Y, Mizuguchi K, Ho RH, Kim RB. Identification of novel functional organic anion-transporting polypeptide 1B3 polymorphisms and assessment of substrate specificity. Pharmacogenet. Genomics. 2011 Mar; 21(3): 103-14. PMID: 21278621, PMCID: PMC3044558, DOI: 10.1097/FPC.0b013e328342f5b1, ISSN: 1744-6880.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/21278621.
- Eckrich MJ, Yang E, Domm J, Ho R, Calder C, Manes B, Bleesing J, Frangoul H. A unique clinical presentation of X-linked lymphoproliferative syndrome with a novel mutation in SH2D1A and review of the literature. J. Pediatr. Hematol. Oncol. 2011 Jan; 33(1): e39-42. PMID: 20975587, DOI: 10.1097/MPH.0b013e3181e75747, ISSN: 1536-3678.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/20975587.
- Ho RH, Leake BF, Kilkenny DM, Meyer Zu Schwabedissen HE, Glaeser H, Kroetz DL, Kim RB. Polymorphic variants in the human bile salt export pump (BSEP; ABCB11): functional characterization and interindividual variability. Pharmacogenet. Genomics. 2010 Jan; 20(1): 45-57. PMID: 20010382, PMCID: PMC2883163, PII: 01213011-201001000-00006, DOI: 10.1097/FPC.0b013e3283349eb0, ISSN: 1744-6880.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/20010382.
- Eckrich MJ, Domm J, Ho R, Whitlock JA, Frangoul H. Autologous stem cell transplant in a patient with Down syndrome and relapsed Hodgkin lymphoma. Pediatr Blood Cancer. 2009 Dec 12/15/2009; 53(7): 1327-8. PMID: 19760777, DOI: 10.1002/pbc.22182, ISSN: 1545-5017.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/19760777.
- Frangoul H, Wang L, Harrell FE, Ho R, Domm J. Preengraftment syndrome after unrelated cord blood transplant is a strong predictor of acute and chronic graft-versus-host disease. Biol. Blood Marrow Transplant [print-electronic]. 2009 Nov; 15(11): 1485-8. PMID: 19822310, PII: S1083-8791(09)00319-X, DOI: 10.1016/j.bbmt.2009.07.001, ISSN: 1523-6536.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/19822310.
- Piro CC, Crossno CL, Collier A, Ho R, Koyama T, Frangoul H. Initial vancomycin dosing in pediatric oncology and stem cell transplant patients. J. Pediatr. Hematol. Oncol. 2009 Jan; 31(1): 3-7. PMID: 19125078, PII: 00043426-200901000-00002, DOI: 10.1097/MPH.0b013e31818b3520, ISSN: 1536-3678.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/19125078.
- Meyer zu Schwabedissen HE, Tirona RG, Yip CS, Ho RH, Kim RB. Interplay between the nuclear receptor pregnane X receptor and the uptake transporter organic anion transporter polypeptide 1A2 selectively enhances estrogen effects in breast cancer. Cancer Res. 2008 Nov 11/15/2008; 68(22): 9338-47. PMID: 19010908, PMCID: PMC2597047, PII: 68/22/9338, DOI: 10.1158/0008-5472.CAN-08-0265, ISSN: 1538-7445.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/19010908.
- Lavin VA, Hamid R, Patterson J, Alford C, Ho R, Yang E. Use of human androgen receptor gene analysis to aid the diagnosis of JMML in female noonan syndrome patients. Pediatr Blood Cancer. 2008 Aug; 51(2): 298-302. PMID: 18454468, DOI: 10.1002/pbc.21591, ISSN: 1545-5017.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/18454468.
- Urquhart BL, Ware JA, Tirona RG, Ho RH, Leake BF, Schwarz UI, Zaher H, Palandra J, Gregor JC, Dresser GK, Kim RB. Breast cancer resistance protein (ABCG2) and drug disposition: intestinal expression, polymorphisms and sulfasalazine as an in vivo probe. Pharmacogenet. Genomics. 2008 May; 18(5): 439-48. PMID: 18408567, PMCID: PMC4043148, PII: 01213011-200805000-00008, DOI: 10.1097/FPC.0b013e3282f974dc, ISSN: 1744-6872.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/18408567.
- Ho RH, Choi L, Lee W, Mayo G, Schwarz UI, Tirona RG, Bailey DG, Michael Stein C, Kim RB. Effect of drug transporter genotypes on pravastatin disposition in European- and African-American participants. Pharmacogenet. Genomics. 2007 Aug; 17(8): 647-56. PMID: 17622941, PMCID: PMC4063287, PII: 01213011-200708000-00009, DOI: 10.1097/FPC.0b013e3280ef698f, ISSN: 1744-6872.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/17622941.
- Bagatell R, Gore L, Egorin MJ, Ho R, Heller G, Boucher N, Zuhowski EG, Whitlock JA, Hunger SP, Narendran A, Katzenstein HM, Arceci RJ, Boklan J, Herzog CE, Whitesell L, Ivy SP, Trippett TM. Phase I pharmacokinetic and pharmacodynamic study of 17-N-allylamino-17-demethoxygeldanamycin in pediatric patients with recurrent or refractory solid tumors: a pediatric oncology experimental therapeutics investigators consortium study. Clin. Cancer Res. 2007 Mar 3/15/2007; 13(6): 1783-8. PMID: 17363533, PII: 13/6/1783, DOI: 10.1158/1078-0432.CCR-06-1892, ISSN: 1078-0432.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/17363533.
- Jones E, Koyama T, Ho RH, Kuttesch J, Shankar S, Whitlock JA, Cartwright J, Frangoul H. Safety and efficacy of a continuous infusion, patient-controlled antiemetic pump for children receiving emetogenic chemotherapy. Pediatr Blood Cancer. 2007 Mar; 48(3): 330-2. PMID: 16304666, DOI: 10.1002/pbc.20711, ISSN: 1545-5009.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/16304666.
- McRae MP, Lowe CM, Tian X, Bourdet DL, Ho RH, Leake BF, Kim RB, Brouwer KL, Kashuba AD. Ritonavir, saquinavir, and efavirenz, but not nevirapine, inhibit bile acid transport in human and rat hepatocytes. J. Pharmacol. Exp. Ther [print-electronic]. 2006 Sep; 318(3): 1068-75. PMID: 16720753, PII: jpet.106.102657, DOI: 10.1124/jpet.106.102657, ISSN: 0022-3565.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/16720753.
- Ho RH, Tirona RG, Leake BF, Glaeser H, Lee W, Lemke CJ, Wang Y, Kim RB. Drug and bile acid transporters in rosuvastatin hepatic uptake: function, expression, and pharmacogenetics. Gastroenterology [print-electronic]. 2006 May; 130(6): 1793-806. PMID: 16697742, PII: S0016-5085(06)00390-8, DOI: 10.1053/j.gastro.2006.02.034, ISSN: 0016-5085.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/16697742.
- Ho RH, Kim RB. Transporters and drug therapy: implications for drug disposition and disease. Clin. Pharmacol. Ther. 2005 Sep; 78(3): 260-77. PMID: 16153397, PII: S0009-9236(05)00225-0, DOI: 10.1016/j.clpt.2005.05.011, ISSN: 0009-9236.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/16153397.
- Calder C, Hays SR, Manes B, Lavin VA, Ho RH, Frangoul H. Successful bone marrow harvest during pregnancy. Bone Marrow Transplant. 2005 Mar; 35(6): 631-2. PMID: 15756288, PII: 1704844, DOI: 10.1038/sj.bmt.1704844, ISSN: 0268-3369.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/15756288.
- Ho RH, Johnson J, Dev VG, Whitlock JA. A novel t(2;20)(q35;p12) in embryonal rhabdomyosarcoma. Cancer Genet. Cytogenet. 2004 May; 151(1): 73-7. PMID: 15120913, PII: S016546080300390X, DOI: 10.1016/j.cancergencyto.2003.08.023, ISSN: 0165-4608.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/15120913.
- Ho RH, Leake BF, Roberts RL, Lee W, Kim RB. Ethnicity-dependent polymorphism in Na+-taurocholate cotransporting polypeptide (SLC10A1) reveals a domain critical for bile acid substrate recognition. J. Biol. Chem [print-electronic]. 2004 Feb 2/20/2004; 279(8): 7213-22. PMID: 14660639, PII: M305782200, DOI: 10.1074/jbc.M305782200, ISSN: 0021-9258.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/14660639.


text:
Perinatal sulfur dioxide exposure alters brainstem parasympathetic control of heart rate
Aims Sulfur dioxide (SO2) is an air pollutant that impedes neonatal development and induces adverse cardiorespiratory health effects, including tachycardia. Here, an animal model was developed that enabled characterization of (i) in vivo alterations in heart rate and (ii) altered activity in brainstem neurons that control heart rate after perinatal SO2 exposure.
Methods and results Pregnant Sprague–Dawley dams and their pups were exposed to 5 parts per million SO2 for 1 h daily throughout gestation and 6 days postnatal. Electrocardiograms were recorded from pups at 5 days postnatal to examine changes in basal and diving reflex-evoked changes in heart rate following perinatal SO2 exposure. In vitro studies employed whole-cell patch-clamp electrophysiology to examine changes in neurotransmission to cardiac vagal neurons within the nucleus ambiguus upon SO2 exposure using a preparation that maintains fictive inspiratory activity recorded from the hypoglossal rootlet. Perinatal SO2 exposure increased heart rate and blunted the parasympathetic-mediated diving reflex-evoked changes in heart rate. Neither spontaneous nor inspiratory-related inhibitory GABAergic or glycinergic neurotransmission to cardiac vagal neurons was altered by SO2 exposure. However, excitatory glutamatergic neurotransmission was decreased by 51.2% upon SO2 exposure. This diminished excitatory neurotransmission was tetrodotoxin-sensitive, indicating SO2 exposure impaired the activity of preceding glutamatergic neurons that synapse upon cardiac vagal neurons.
Conclusions Diminished glutamatergic, but unaltered inhibitory neurotransmission to cardiac vagal neurons provides a mechanism for the observed SO2-induced elevated heart rate via an impairment of brainstem cardioinhibitory parasympathetic activity to the heart.
- Autonomic nervous system
- Electrophysiology
- Neurotransmitters
- Parasympathetic
- Tachycardia
1. Introduction
The 1952 London Smog incident resulted in over 12 000 deaths due to elevated ambient air pollution levels and was one of the principal events to shed light on the deleterious effects of air pollution on human health.1,2 In 2002, the World Health Organization estimated that 3 million people die annually from the combined health effects of exposure to polluted air, despite the existence of clean air regulations around the world.3 Of the six defined air pollutants in the USA [carbon monoxide, lead, nitrogen oxides, ozone (O3), particulate matter (PM), and sulfur dioxide (SO2)], the roles of O3 and PM in disrupting cardiorespiratory function have been well documented.4 Although studies have shown an increased risk for cardiorespiratory-related death following exposure to SO2, the mechanism(s) responsible, as well as the site(s) of action, have not been thoroughly investigated.5,6
SO2 is a gaseous air pollutant that is readily solubilized upon entering the airways, dissociating into its derivatives, bisulfite and sulfite, triggering free radical formation, and inducing tissue damage and bronchoconstriction.7 In addition to pulmonary toxicity, exposure to SO2 has many known cardiovascular effects including hypertension,8 tachycardia or a decrease in the inter-beat interval of heart rate (HR),9,10 myocardial infarction, and cardiac-related morbidity and mortality.4 While it has been suggested that some of these effects may result from inflammatory events following inhalation, another likely possibility is that SO2 alters cardiorespiratory activity by varying cardiac function through alterations to the autonomic nervous system. Indeed, SO2 exposure elevates HR and induces autonomic imbalance to the heart, particularly by diminishing parasympathetic cardioprotective activity.10,11
While known adverse physiological effects of SO2 exposure have been examined primarily in adult populations, the Environmental Protection Agency has stated that neonates, a particularly sensitive subpopulation, have so far been ignored in physiological studies.12 Previous work has linked prenatal air pollution exposure to several adverse birth outcomes including intrauterine growth restriction, very low birth weight, and congenital heart defects.13–15 A strong link between SO2 exposure and sudden infant death syndrome (SIDS) has also been shown.16 A peak in pollutant levels during the winter months increased the number of SIDS cases with a 7-week delay suggesting prenatal SO2 exposure increases the risk of SIDs. Other work has confirmed the finding that SO2 exposure is correlated with SIDS and showed an 8.49% increase in the incidence of SIDS for every inter-quartile increase in SO2 levels.17 Given the impacts of SO2 on the cardiorespiratory system, and that SIDS results from cardiopulmonary collapse, research examining the impact of perinatal SO2 exposure on cardiorespiratory function is highly warranted.
Owing to the lack of focus on neonatal cardiovascular health, we herein developed a novel animal model of perinatal SO2 exposure and characterized the in vivo effects of SO2 on parasympathetic control of HR, as well as alterations in the cellular changes in brainstem neurons that control HR, which are a likely target for these adverse cardiovascular consequences.
2. Methods
Experiments were performed on Sprague–Dawley rats (Hilltop Lab Animals, Inc., Scottdale, PA, USA) housed in The George Washington University (GWU) animal care facility. All animal procedures were approved by the GWU Institutional Animal Care and Use Committee, and all procedures are in accordance with the recommendations of the Panel on Euthanasia of the American Veterinary Medical Association and the National Institutes of Health publication Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health (NIH Publication, 8th Edition, 2011). Rats were maintained under standard environmental conditions (12:12 h light:dark cycle) with free access to food and water.
2.1 SO2 exposure protocol
Starting on the first day of gestation through 6 days postnatal (P6), pregnant rats (and their pups) were exposed to 5 parts per million (p.p.m.; 13.1 mg/m3) SO2 for 1 h daily. This concentration was selected based on previously published studies in which 5–10 p.p.m. was selected to mimic urban atmospheres,7,18 as well as the Occupational Safety and Health Administration Short-Term Exposure Limit (STEL) of 5 p.p.m., which is the maximum 1 h personal exposure limit.19 A Single Toxic Gas Monitor for SO2 (RKI Instruments, Union City, CA, USA) was used to monitor the concentration of SO2 inside a sealed chamber (E-Z Systems, Palmer, PA, USA). In control experiments the same exposure protocol was used except animals were exposed to medical-grade air. SO2 and medical-grade air tanks were purchased from Roberts Oxygen (Rockville, MD, USA).
2.2 Unrestrained ECG recording
Three standard electrocardiogram (ECG) electrodes were affixed to unanaesthetized and unrestrained P5 pups in the Lead II configuration, and ECG activity was amplified (CWE, Inc., Ardmore, PA, USA), digitized and recorded using the DSI Ponemah software (St Paul, MN, USA). The effect of SO2 exposure on basal and reflex control of HR was examined by eliciting the diving reflex, a powerful parasympathetic reflex resulting in bradycardia,20 by placing one to two drops of cold (10°C) water on the pup's nose. Atropine sulfate (1 mg/kg, sc)21 was subsequently injected to block parasympathetic activity, and the reflex was retested. Atenolol (10 mg/kg, sc)21 was then administered to additionally block the sympathetic control of HR to determine intrinsic HR. Pups were kept on a heating pad to ensure stable body temperature at 34°C. Atropine sulfate and atenolol were received from Sigma-Aldrich (St Louis, MO, USA). None of the pups used for ECG recordings underwent any surgical procedures.
2.3 Labelling of cardiac vagal neurons and slice preparation
In a separate group of animals, pups at P1 were anaesthetized via hypothermia and cooled to ∼4°C. Once HR significantly slowed and no pain reflex was elicited, a right thoracotomy was performed to expose the heart, and the retrograde tracer rhodamine (XRITC, Invitrogen, 2% solution, 20–50 μL) was injected into the pericardial sac to label cardiac vagal neurons (CVNs). Following the surgery, buprenorphine (0.1–0.5 mg/kg) was immediately administered sc and pups were warmed to raise their body temperatures on a heating pad. Pups were monitored for 30 min and every 20 min thereafter until ambulatory, and two more injections of buprenorphine were given within the next 2–12 h.
After 3–5 days of recovery, animals were overdosed with isoflurane and euthanized by cervical dislocation. Brain tissue was collected and placed in 4°C physiological saline buffer solution with the following composition: NaCl (140 mM), KCl (5 mM), CaCl2 (2 mM), glucose (5 mM), and HEPES (10 mM). The medulla was dissected to preserve the hypoglossal cranial rootlets, mounted on a cutting block, and placed into a vibrating blade microtome. A single slice (800 µm) that included the rostral ventral lateral medulla, the hypoglossal nerve rootlet, and the nucleus ambiguus was obtained and submerged in a recording chamber that allowed perfusion above and below the slice with room temperature artificial cerebrospinal fluid with the following composition: NaCl (12 5 mM), KCl (3 mM), CaCl2 (2 mM), NaHCO3 (26 mM), glucose (5 mM), HEPES (5 mM) in equilibrium with 95% O2–5% CO2. The osmolarity of all solutions was 285–290 mOsm, and the pH was maintained between 7.35 and 7.4.
2.4 Recording respiratory network activity and patch-clamp techniques
The thick medullary slice preparation generates rhythmic inspiratory-related motor discharge in hypoglossal cranial nerves.22 Spontaneous respiratory-related activity was recorded by monitoring motorneuron population activity from the hypoglossal rootlets using a suction electrode. Hypoglossal nerve rootlet activity was amplified (50 000×), filtered (10–300 Hz pass; CWE, Inc., Ardmore, PA, USA), and electronically integrated ([tau] = 50 ms; CW).
CVNs were identified by the presence of the fluorescent tracer and differential interference contrast optics along with infrared illumination and infrared-sensitive video detection cameras to gain enhanced spatial resolution. Patch pipettes were filled with a solution at pH 7.3 consisting of either KCl (150 mM), MgCl2 (4 mM), EGTA (10 mM), Na-ATP (2 mM), HEPES (10 mM) or K-gluconic acid (150 mM), HEPES (10 mM), EGTA (10 mM), MgCl2 (1 mM), CaCl2 (1 mM) to isolate for inhibitory or excitatory currents, respectively. Identified CVNs were voltage-clamped at a holding potential of −80 mV.
2.5 Drug application
All drugs used in these experiments to isolate neurotransmission were applied using a pneumatic picopump pressure delivery system (WPI, Sarasota, FL, USA). Drugs used include gabazine (25 µM) to block GABAergic inhibitory neurotransmission, strychnine (1 µM) to block glycinergic inhibitory neurotransmission, and d(−)-2-amino-5-phosphopentanoic acid (AP5; 50 µM) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 50 μM) to block all excitatory neurotransmission.
In experiments where miniature excitatory postsynaptic currents (mEPSCs) were isolated, the voltage-gated sodium channel blocker tetrodotoxin (TTX; 1 μM) was included in the perfusate. All drugs were received from Sigma-Aldrich (St Louis, MO, USA).
2.6 Data analysis
To determine baseline HR, the 15 s prior to diving reflex stimulation was divided into 5 s bins and the average R–R interval for each bin was used to determine HR using the Ponemah Standard ECG Analysis Software (DSI, Minneapolis, MN, USA). The change in HR upon evoking the diving reflex was obtained within 5–10 s after placing one to two drops of cold water on the nose before and after atropine sulfate administration to block parasympathetic activity to the heart. To determine intrinsic HR atenolol was also administered to block sympathetic activity to the heart. Averages for baseline HR, change in HR with and without atropine sulfate, and intrinsic HR were compared between control and SO2-exposed animals. Recordings were considered outliers based upon the very conservative estimation of being >8 SD away from the mean.
Previous work in the laboratory has demonstrated that CVNs exhibit respiratory-related activity via coupling of inhibitory postsynaptic currents (IPSCs) to fictive inspiratory activity recorded from the hypoglossal motor nerve rootlet.23 Before and after each fictive inspiratory burst, 5 s of data were taken and binned into 1 s averages. Data were obtained and then averaged from the first five bursts from each cell.
Spontaneous EPSCs and mEPSCs were recorded for at least 5 min. To determine the frequency of EPSCs, the number of excitatory events was divided by the duration of the recording. Data were obtained and averaged under each condition.
MiniAnalysis (Synaptosoft version 4.3.1) was used to analyse all experimental traces. The threshold for GABAergic, glycinergic, and glutamatergic events was set to five times the root mean square of noise. When multiple cells per animal were used for electrophysiology experiments, the frequency of postsynaptic currents was averaged into a single value for that animal. The averaged data and comparisons between groups included only one data value per animal, with the n-value equal to the total number of animals used for that series of experiments or condition. All data are represented by mean ± SEM. A repeated-measures two-way ANOVA was used to determine statistical significance for the inspiratory-related activity. A Bonferroni post hoc test was used to determine statistically significant differences with a P-value <0.05. A two-tailed unpaired Student's t-test was used to determine statistical significance for the frequency of excitatory events, as well as HR. An F-test was used to determine whether equal variance or unequal variance was used for the t-test, and statistical significance was determined with a P-value <0.05.
3. Results
3.1 Perinatal SO2 exposure elevates HR and blunts reflex activation of parasympathetic activity
To determine the effect of perinatal SO2 exposure on baseline HR, ECGs were recorded from P5 rat pups, as shown in Figure 1. HR, recorded from unanaesthetized and unrestrained pups, was significantly elevated (P < 0.05) following SO2 exposure (424 ± 9 b.p.m.; n = 10) compared with control animals (374 ± 12 b.p.m.; n = 11), an increase of 13.4% (Figure 1B). To determine whether or not reflex changes in parasympathetic activity to the heart were altered by SO2, ECGs were recorded during the activation of the diving reflex, which is a powerful parasympathetic reflex that results in bradycardia after cold water has been placed on the pup's nose (Figure 1C).20 Here, the activation of the diving reflex produced a robust decrease in HR of 43 ± 6 b.p.m. (P < 0.05; n = 11). Atropine sulfate, a muscarinic receptor antagonist, blocked the diving reflex as exhibited by a decrease in HR of only 2 ± 1 b.p.m. (P > 0.05; n = 11). However, in SO2-exposed animals, diving reflex activation decreased HR by only 18 ± 6 b.p.m. (P > 0.05; n = 10), a significant decrease in reflex-evoked changes in the HR, which was also abolished following atropine sulfate injection (2 ± 1 b.p.m.; P > 0.05; n = 10). Together, these data indicate that perinatal SO2 exposure produces a blunting of reflex control of parasympathetic activity (Figure 1E). Additionally, isolation of intrinsic HR, following combined injection of atropine sulfate and the β1-antagonist atenolol, showed that perinatal SO2 also significantly elevated intrinsic HR (266 ± 7 b.p.m.; n = 10) compared with control animals (208 ± 10 b.p.m.; n = 11; P < 0.05; Figure 1D), suggesting an additional mechanism by which SO2 results in an elevated HR.
Litters were also observed for changes in litter size and average weight at birth. The average litter size for control litters was 13.8 ± 1.3 pups, and for SO2-exposed litters were 14.1 ± 1.0 pups; these differences are not significant. The average weight at birth for control pups was 5.9 ± 0.2 g, and for SO2-exposed pups was 6.2 ± 0.3 g. These differences were also not significant.
3.2 Perinatal exposure to SO2 does not alter inhibitory neurotransmission to CVNs
The cardiovascular effects of SO2 exposure in humans have been hypothesized to be due to a loss of vagal, or parasympathetic, activity.10 The in vivo recordings from our rat model indicate SO2 exposure mimics the cardiovascular changes seen in epidemiology studies, suggesting that this is a viable model to examine the mechanisms that underlie the diminished parasympathetic drive to the heart that occurs with SO2 exposure. Parasympathetic activity to the heart originates from premotor parasympathetic neurons in the brainstem; since these neurons are inherently silent, the synaptic activity to these neurons is a critical determinant of their activity. To determine the mechanism(s) responsible for altered excitability, neurotransmission to premotor CVNs that control HR was studied. We tested whether the diminished parasympathetic activity to the heart was due to an increase in inhibitory and/or decrease in excitatory neurotransmission to CVNs. The following electrophysiological experiments were obtained from a total number of 61 pups from 15 dams (controls: 28 pups from 8 dams; SO2 exposures: 33 pups from 7 dams).
Previous work has demonstrated that CVNs possess respiratory-related patterning consisting of increases in both GABAergic and glycinergic IPSCs during inspiratory activity recorded from the hypoglossal (XII) rootlet.23 Upon isolation of GABAergic IPSCs (Figure 2), perinatal exposure to SO2 was found to have no significant (P > 0.05) changes in GABAergic neurotransmission to CVNs during either spontaneous (control, 6.4 ± 0.9 Hz, n = 6 animals; SO2, 6.9 ± 0.8 Hz, n = 5 animals) or inspiratory-related (control, 11.1 ± 1.3 Hz; SO2, 11.9 ± 0.7 Hz) neurotransmission. Similarly, glycinergic IPSCs also showed no significant (P > 0.05) differences in IPSC frequency between control and SO2-exposed pups during both spontaneous (control, 7.2 ± 1.0 Hz, n = 4 animals; SO2, 6.1 ± 0.8 Hz, n = 5 animals) and inspiratory-related (control, 11.9 ± 1.3 Hz; SO2, 11.6 ± 1.5 Hz) activity, as shown in Figure 3.
3.3 Perinatal SO2 exposure alters excitatory signalling to CVNs
While inhibitory neurotransmission to CVNs is known to mediate respiratory sinus arrhythmia, excitatory neurotransmission does not exhibit inspiratory-related coupling. Instead, glutamatergic activity to CVNs is thought to be responsible for generating the basal activity in parasympathetic premotor CVNs and HR changes that occur upon the activation of chemoreceptor and baroreceptor reflexes.24 Spontaneous glutamatergic EPSCs were significantly (P < 0.05) diminished in SO2-exposed animals (2.1 ± 0.3 Hz, n = 11 animals) compared with control (4.3 ± 0.8 Hz, n = 5 animals) pups, a decrease of 51.2%, as shown in Figure 4A and B.
To determine whether this impaired excitatory neurotransmission was due to dysfunction of the presynaptic release of neurotransmitters, or was action potential-dependent, the voltage-gated Na+ channel blocker TTX was included in the perfusate. The resulting mEPSCs in CVNs were recorded, and the prior difference in the frequency of excitatory neurotransmission between the two groups of animals was abolished, as shown in Figure 4C. Instead, mEPSC frequency in control (2.1 ± 0.6 Hz, n = 5 animals) and SO2-exposed animals (2.3 ± 0.2 Hz, n = 6 animals) were not significantly different. These results indicate that the decrease in glutamatergic neurotransmission to CVNs following SO2 exposure is action potential-dependent and is likely due to alterations in the activity of the preceding neurons in the cardiorespiratory network, rather than to changes in the function of the presynaptic glutamatergic terminals surrounding CVNs.
4. Discussion
Neonates are a poorly studied subpopulation in air pollution physiology, despite traditionally possessing increased sensitivity to several toxins. To the best of our knowledge, we have herein developed the first animal model for investigating SO2 toxicity in this age group. As such, there are three main findings in this study: (i) Our novel animal model of SO2 exposure mimics the cardiovascular effects seen in humans and is the first to focus solely on the effects of perinatal exposure. (ii) While inhibitory neurotransmission to CVNs was unchanged, SO2 significantly reduced glutamatergic EPSC frequency in a TTX-dependent manner, indicating the site of action of SO2 exposure is likely on excitatory glutamatergic neurons and pathways prior to CVNs in the brainstem cardiorespiratory network. (iii) Air pollution exposure is often associated with respiratory disease, but results presented here suggest additional targets, particularly autonomic parasympathetic activity within the brainstem.
This study has shown that perinatal exposure to SO2 increases baseline HR, which in combination with the blunted reflex control of parasympathetic activity demonstrated in the in vivo experiments, elevates the risk of cardiovascular death among a traditionally at-risk subpopulation. Given that SO2 is associated with cardiorespiratory morbidity and mortality in adult populations,4 the physiological data shown here may provide a mechanistic link between SO2 exposure and adverse cardiovascular events. While further work is necessary to identify the alterations in the reflex pathways to CVNs, the results in this study lay the foundation for understanding the diminished parasympathetic activity to the heart in neonates following SO2 exposure.
Several epidemiological studies have examined the effects of SO2 on the adult population, leading to a number of hypotheses about how SO2 alters parasympathetic regulation of the heart. However, the lack of an animal model has hindered further investigation into the mechanism(s) disrupting cardiovascular regulation following exposure. The goal of this study was to test and develop an animal model that would not only facilitate research into the cellular changes arising from SO2 exposure, but would also address the question of whether or not physiological activity is altered by perinatal exposure. In this animal model, Sprague–Dawley rats were exposed during gestation and through 6 days postnatal to 5 p.p.m. SO2 for 1 h daily. The results of this study show SO2 exposure elicits an increase in basal HR, a loss of parasympathetic drive to the heart, and an increase in intrinsic HR. Increases in HR and decreases in cardioprotective parasympathetic activity increase susceptibility to arrhythmia development and cardiovascular disease.25–30 These alterations are likely responsible for many cardiovascular-related deaths and adverse events following SO2 exposure worldwide.
Using the perinatal model developed in this study, we applied in vitro electrophysiology techniques to elucidate a novel mechanism of action for SO2 exposure in brainstem cardiovascular function. Parasympathetic regulation of HR is mediated by CVNs originating in the nucleus ambiguus, and is modulated by both inhibitory and excitatory neurotransmission to these cells.31 Previous work has shown that IPSCs are responsible for inspiratory-related changes in parasympathetic activity to the heart,23 while EPSCs are essential for generating on-going tonic parasympathetic activity.24 Based on our in vivo results, and similar findings by others, we hypothesized SO2 would diminish inspiratory-related inhibitory inputs to CVNs but were surprised to find no differences in either the spontaneous or inspiratory-related activity of neither GABAergic nor glycinergic IPSCs between control and SO2-exposed animals. However, SO2 exposure did significantly diminish glutamatergic EPSCs in CVNs. This loss of excitatory neurotransmission to CVNs would be responsible for a withdrawal of parasympathetic cardioinhibitory vagal activity to the heart, resulting in an elevated basal HR, both of which were present in in vivo recordings from P5 pups.
TTX blocks the activity of voltage-gated Na+ channels, preventing the propagation of action potentials along the axon and isolating action potential-independent mEPSCs, which are thought to be spontaneous release of neurotransmitter from vesicles at presynaptic terminals. The results presented here show mEPSCs in CVNs were not different in animals exposed to SO2, indicating SO2 exposure likely decreases activity of preceding glutamatergic neurons that project to CVNs rather than modifying the presynaptic function. Because SO2 is an inhaled pollutant known to induce bronchoconstriction in animal models of chronic bronchitis,32,33 we suggest that future studies should consider testing the hypothesis that SO2 acts on laryngeal receptors via a multisynaptic pathway to reduce glutamatergic activity in CVNs.
In the late 1990s, several epidemiological studies examined the impact of air pollution exposure on various indicators of cardiovascular health; however, most of this research focused predominately on PM and O3. In 1999, Pope et al.34 published a critical finding linking PM exposure to an altered autonomic state, including tachycardia. This work was quickly followed by more research into air pollution epidemiology, and in the same year Peters et al. published results from an episode in Augsburg, Germany, linking elevated ambient pollution levels to tachycardia in the adult population. These initial studies have been followed by several others examining air pollution events and their impact on measures of cardiovascular health.9,35 It is clear that at least one mechanism by which SO2 exposure disrupts cardiovascular function is through autonomic dysregulation; however, it is still unclear whether these effects are due to an inflammatory response or to stimulation of airway receptors.
A 2006 study by Routledge et al.10 aimed to answer this question using short-term exposure to SO2 in healthy humans. A loss of vagal activity and a lack of circulating inflammatory markers 4 h after exposure suggested that SO2 acts on airway receptors to disrupt neurological inputs to the parasympathetic nervous system. This hypothesis has been echoed and further supported by others arguing that work examining the mechanism behind this evolving hypothesis is needed to advance the field.5 The development of the novel animal model here plays a significant role in achieving that objective. Not only has a new tool been developed, but it has also allowed us to identify pivotal foundations underlying the loss of cardioprotective parasympathetic activity following SO2 exposure. Importantly, work shown here also suggests an additional mechanism of SO2 may be responsible for increasing intrinsic HR, which is an area that should be investigated in future studies. In this study, we have shown that upon inhalation SO2 decreases excitatory inputs to CVNs, likely by depressing a multisynaptic pathway, and hypothesize that this is likely done through the activation of reflexes originating from laryngeal airway receptors. The subsequent vagal withdrawal increases HR, placing the individual at risk for sudden cardiac death.35,36
This work was supported by the National Institutes of Health (HL49965, HL59895, and HL72006 to D.M.); and the GW Institute for Sustainability Research, Education, and Policy Research Award to A.L.W.
A.L.W. is a predoctoral student in the Molecular Medicine Program of The Institute for Biomedical Sciences at The George Washington University. This work is from a dissertation to be presented to the above program in partial fulfilment for the PhD degree.
Conflict of interest: none declared.
- Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2013. For permissions please email: email@example.com.

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This is a great deal on this magazine! It has so many interesting recipes and insight on how to remodel or redo your home! Great magazine to have on my coffee table!


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EUGENE -- Oregon's eighth practice is over, meaning spring football has moved past the halfway point until the May 3 spring game. Here were some of today's quick hits from practice:
-- I asked defensive coordinator Don Pellum about Oregon's drop in tackles for loss the last two seasons, and whether it was a concern. He said it was, but wasn't getting worked up about where to point the finger.
Oregon had 94 tackles for loss in 2011, 84 in 2012 and 70 last season. In 2011-12, Oregon enjoyed the services of blitz specialists in Michael Clay and Kiko Alonso at the two inside linebacker spots, and Pellum said Alonso's instincts are hard to replicate.
"He had more of a green light" to blitz if he read a key correctly, Pellum said, adding that second-year inside 'backer starters Derrick Malone and Rodney Hardrick don't have that kind of green light yet.
-- Alonso and Clay, incidentally, watched practice today. Clay was hired in January as a defensive quality control coach for the Philadelphia Eagles by his former coach, Chip Kelly. Alonso, of course, had a terrific rookie season at linebacker for the Buffalo Bills.
-- The other news of the day was player and coaches' reactions to the NCAA recommendation that student-athletes be allowed unlimited food by their universities. That would be a dramatic change from the one meal a day currently allowed by training tables.
Mark Helfrich quipped that it would be of most benefit to "walk-on linemen's parents" because of how much linemen eat and how walk-ons are excluded from training tables unless they pay (at Oregon, it costs them $8.72 a meal).
As you might expect, offensive lineman Tyler Johnstone was overjoyed by the news, saying his $1,200 scholarship check each month is difficult to budget.
-- We'll have videos and galleries and some stories this afternoon from practice. The media can talk with Johnathan Loyd for the first time this spring at 3 p.m. this afternoon, so I'll have a story about that afterward.


text:
Four Southern California men held in plot to join al-Qaida, Taliban (Los Angeles Times)
House explosion in Indiana now being treated as a homicide (Indianapolis Star)
Police make arrest in beating death of monkey at Boise, Idaho, zoo (Idaho Statesman)
Record rain swamps Puget Sound area in Washington (Seattle Times)
Big news from Mars? Rover scientists are mum for now (NPR)
Bias weighed as motive in killings of three Brooklyn shopkeepers (New York Times)
Massachusetts to widen tuition breaks to include immigrants (Boston Globe)
Marine base in Arizona to introduce first operational F-35 squadron (Yuma Sun)
Court rejects Hobby Lobby's challenge to contraceptive mandate (Reuters via Chicago Tribune)
Santa Monica may bar nativity scenes in public areas, judge rules (Los Angeles Times)
New York police officer accused of plotting kidnapping, cannibalism pleads not guilty (New York Daily News)
Outdoor forensic 'body farm' to open in western Colorado (TheDenverChannel.com)
Grocery store gives customers free groceries after computer glitch prevents checkout (Charlotte Observer)
Chicago woman accused of using stun gun to rob mother of $40,000 ring (CLTV.com)
Town in Alaska gets new harbor with no road offering access to it (Anchorage Daily News)
World news
Efforts for ceasefire stepped up in Gaza (BBC)
Barrage of 16 rockets fired at Israeli city; nine intercepted (Jerusalem Post)
Senator says Obama deserves credit for 'Iron Dome' protecting Israel (National Review via Yahoo! News)
Tensions loom as President Obama meets Asian leaders (Reuters)
Islamists reject Syrian rebel group as EU embraces it (Wall Street Journal)
Extortionist to serve 10 years in prison for fake collar bomb (CNN)
China must address corruption or face 'seething anger,' incoming president warns (London Telegraph)
Congo forces and rebels resume fighting for Goma (New York Times)
Festival stampede kills at least 14 in India (BBC)
Drunken Australian man tries to ride a crocodile (BBC)
Man handed out cocaine by mistake to trick-or-treaters (London Guardian)


text:
As Israel and Hamas resumed launching rockets today, a group of Syrian-Americans took to the streets in Allentown to plead for peace.
Several dozen people gathered and spoke during a rally against the continued violence in Gaza, which took place at Catasauqua and Fullerton avenues in Allentown near the St. George Orthodox Church.
Khaldoun Makhoul, chairman of the Pennsylvania chapter of the Syrian American Forum, helped organize the event to raise awareness and support for the Palestinian people and the need for a two-state solution with Israel.
Makhoul said even though he is not Palestinian, the nearly three weeks of fighting between militants and the Israeli military has a direct effect on the entire region.
Meanwhile, the Syrian civil war saw 1,700 people die this week, the deadliest seven-day period since the war began more than three years ago. Something has to change and the violence needs to stop, Makhoul said.
"The solution should be for the whole area. Peace should be for the whole area," Makhoul said. "We don't want to see fighting anymore. We want to live in peace."
Makhoul cautioned U.S. legislators against giving money to "carefully vetted moderate" Muslim organizations when, in fact, they turn out to be radical groups.
The SAF supports last month's election of Syrian President Bashar al-Assad and asks that the U.S. respect the election results. Critics have questioned the validity of the election that showed Assad winning 88.7 percent of the vote.
Makhoul, a Christian who moved to the U.S. in 1994 from Syria to pursue his medical career, said the anti-Assad Islamic State of Iraq and Syria has been targeting Christians in Syria and he fears for his family still living there.
SAF member Fayez Abboud lives in Allentown and said he attended Sunday's rally to tell Americans that supporting the Palestinian people and ending the violence is the moral thing to do regardless of religious affiliation.
"I am a Christian Arab but I have to be against what is happening in Gaza," Abboud said. "We have to stand united: Muslims, Jews, everyone against violence. It's our responsibility as humans to stand side by side and say, 'That's it. It has to stop.'"
Makhoul said he sees the people of Syria, Lebanon, Iraq and Palestine as one people and if Palestine does not find a solution with Israel, then there will continue to be problems in the entire Middle East and there will never be peace.


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What does the HIV virus bind to that makes the patient susceptible to secondary infections?
CD 4 on Helper T cells (no directions are given to other WBC)
What makes up the core of a virus?
Nucleic acid - DNA or RNA in any form (single, double, fragmented)
How do viruses that are enveloped helical viruses obtain their envelope?
when leaving the host cell they obtain it
What are the spikes on an enveloped helical virus for and what are they made of?
For attachment and detachment, made of Protein and glycoproteins
What is an additional function of the spikes on an enveloped helical virus besides attachment and detachment?
Agglutination - clumping of the hosts cells
What are some ways that we are able to study viruses?
Human tissue samples
HeLa - Cancerous cells used from 1950's
What is the stages of the Lytic cycle?
1. Attachment
2. Penetration
3. Biosynthesis
4. Maturation
5. Release
What phase of the Lytic cycle requires the use of the lysozyme?
Insertion (ONLY FOR BACTERIOPHAGES INFECTING BACTERIA)
What phase of the Lytic cycle requires the host making the viruses parts and chopping up the viruses DNA?
What occurs to the genetic material of a cell when it is invaded during a lysogenic cycle?
Genetic recombination (viral nucleic acid incorporates into host genome)
What is the viruses called once its nucleic acid has invaded a bacteria's genome during the lysogenic cycle?
What is a cell called once it has been invaded during the lysogenic cycle and its genome has been invaded by the viruses nucleic acid and the cell remains inactive?
Latent prophage (person could be asymptomatic)
What are the three results of Lysogenic infection?
1. Immunity to reinfection by the exact same virus
2. Phage conversion
3. Specialized transduction
What are some examples of bacteria that require phage conversion to be effective?
C. botulinum
What result of Lysogenic infection results in the host cell being converted by the phage's DNA?
Phage conversion
What is a result of lysogenic infection that results in a genetic transfer?
Specialized transduction (host cell is changed because it acquired the bacterial genes carried from the virus)
What happens to the viruses envelope during exocytosis?
Creates the envelope by taking some of the host's cell membrane with it
What is the stage during viral replication in Eukaryotes when the virus uses the hosts cell's organelles to make more core and capsid?
What does the virus turn the host cells' RNA polymerace into?
Transcriptase (same thing, just different name)
What is something unique about RNA in viruses?
They can have additional + and - strands, called sense and antisense strands
What are the 3 functions of RNA + strands?
1. Can serve as mRNA
2. Can serve as core in newly created virus
3. serve as a template to make more core
What are the first three herpes viruses names and causes?
1. HHV1/HSV1 - fever blisters/cold sores
2. HHV2/HSV2 - Genital herpes
3. HHV3/HSV3 - Varicella - Zoster
Herpes - Zoster
Chicken pox - shingles
What are the 4th-8th herpes viruses?
4. HHV4 - (Mono) Lymphocrypto virus
Epstein Barr Virus
> Burkitts Lymphoma (jaw cancer)
>Nasopharyngeal Carcinoma (nose and throat cancer)
5. HHV5 - CMV (Cytomeglia Virus)
6. HHV6 - Roseola
7. HHV7 - Roseola
8. HHV8 - Kaposis Sarcoma (cancer - HIV patients are prone to getting)
What makes Hep C concerning as far as its ability to be stable in O2?
Transmission through respiration
What are some of the external changes that can occur to a cell after it has been infected by a virus?
1. loss of contact inhibition (cause excessive growth with no function)
2. Syncytium (fusion of the cells)
3. Permeability changes
4. Ag change (so immune either ignores cell or attacks it)
5. Interferons
What are some of the internal changes that can occur to a cell after it has been infected by a virus?
1. Inclusion bodies
2. DNA changes
3. Changes in cellular functions
What is the function of Alpha and Beta interferons?
They are released by infected cells to warn healthy ones so they will build intercellular antiviral proteins
What is the defense mechanism the body has with healthy cells if they have been warned of infection by alpha and beta interferons?
Build intracellular antiviral proteins
What are some of the change to DNA that viruses can make?
Turn genes on and/or off and mutate the genes
What is the effect of polio on a cell?
Interferes with the lysosomes (the digestive enzymes in a cell)
What is a method for studying bacteriaphages by looking at the clearings they create on a bacteria lawn?
What is used for studying viruses that allow the virus to proliferate and shows the tissues it attacks?
Embryonic eggs
What are the three main functions of the lymphatic system?
1. Immunity
2. Pick up fats and lipid soluble vitamins and returns it to the blood (Vit A, D, E, K)
3. Pick up lost tissue fluid and returns it to the blood
What is a bubble of lymph that creates movement of the lymph when the diaphram pushes on it?
Cisterna chyli
what percentage of WBCs does Monocytes, Eosinophils, and Basophils make?
5% in decreasing order - M, E, B
if there is no infection and macrophages arrive, what are two things that could happen to them?
they either die or cause an autoimmune response by attacking the healthy cells
how do Natural Killer cells attack a virus?
shoot cytotoxic chemicals (but not as accurately as T cytotoxic cells)
what do Eosinophils attack and cause?
-parasitic worms
-a part of allergic reactions
-eat Ag/Ab complexes
-cause oxidative burst
why do a lot of RBCs accumulate in the spleen?
they are old and about to be destroyed but are kept there in case of major blood loss (still functional)
what are the forms of non-specific defence?
physical and chemical barriers (1st line)
complement proteins (2nd line)
what are some of the physical barriers our body has to keep out pathogens?
-flushing mechanisms (includes sweat, tears, oil, vomiting, defecation, urination, and cilia)
-our own microbes
what are some of the chemical barriers our body uses to keep out pathogens?
-high salt content of our skin
-acids (in sweat oil, vaginal fluids)
-lysozymes (destroys cell membranes and is in sweat and tears, also includes IgG)
when is the Ab IgG used in non-specific defense and when is it used in specific defense?
non-specific if in body secretions
specific if in the blood
what isq it called when T cells that have failed their education a "shot on sight"?
destruction apoptosis
what is it called when failed T cells are released with a lack of ability to respond, and pose no threat?
what vaccine is given to prevent B. Pertussis, and what protein is injected with the vaccine?
D Tap, includes acellular pertussis and the protein Tetnus
what are the three initial pathways that lead to the common pathway?
Classical pathway
Alternative pathway
Lectin pathway
What complement protein is activated in the common pathway and what happens to it?
C3 divides into C3a and C3b
what does complement protein C3 cause when it becomes C3b?
Opsonization and MAC (membrane attack complex)
what are the two chemicals that blow up the membrane or the nucleus of a germor infected cell?
perforin and granulysins
what are the four different types of immunity?
active natural
passive artificial
active artificial
passive natural
What are some other names for Antibodies?
Immunoglobulins (Ig) and Gamma Globulin Glycoproteins (GGGP)
Whare the functions of IgM?
-First to arrive at the site of infection
-An agglutinator
-Fixes (stimulates) complements
What are the functions of IgG?
-Activates natural killer cells
-Fixes complement
-Most abundant in blood stream
-Primary Ab in secondary exposure to Ag "Desensitizing"
What is different about the clones of the T helper cells?
Have receptors that match the complex better
What are two chemicals that T cells release?
Perforin - Pokes holes in CM or CW
Lymphotoxin - blows up nucleus
Gamma Interferons (G-IFN) - elicit the phagocytes
What are the four types of autoimmune responses?
1. Anaphylactic
2. Cytotoxic/Transfusion
3. Immune complex
4. Transplantation/Cell-mediated
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text:
Connecticut's Unemployment Remains High But There Are Jobs to Be Found
For every job opening in Connecticut, there are nearly six people who are unemployed.
The fact that some companies are struggling to find qualified candidates for the more than 25,000 jobs posted on the Connecticut Department of Labor's website is one of the more frustrating factors contributing to Connecticut's 8.2-percent unemployment rate in the first half of the year. If all of these jobs were filled by some of the state's 152,000 unemployed, the state's unemployment rate would drop by a full percentage point or more, bringing it below the national average of 7.6 percent.
Connecticut was recently characterized by a right-wing Forbes columnist as having one of the nation's "worst-performing" economies, and the state was ranked last in economic growth by the U.S. Department of Commerce Bureau of Economic Analysis.
Click here to see a larger version of the infographic at right.
"The economy is improving, but it's still at sub-par growth," says Peter Gioia, an economist and vice president at the Connecticut Business & Industry Association. "The economy obviously still has some significant challenges to it, but that doesn't deny the fact that we are growing."
Connecticut added jobs in five out of 2013's first six months. Gioia says they aren't necessarily the same jobs the state had before the economic downturn, nor are they all great-paying jobs or positions where people's skills are used to their best potential. And while unemployment has declined, the drop isn't completely due to more people finding work. Some have just stopped looking for a job or decided to retire.
"There are a lot of jobs that are gone that are not coming back," says Gioia. "But now there are unmet and unfilled needs that are out there in the workforce, so we also have a problem of mismatching—who's looking for jobs and what jobs are available."
Manufacturing is one economic sector where hiring continues, Gioia notes, and often provides well-paying jobs. Like other areas of the economy, manufacturing is still recovering—but the industry is nearing a time when many of the most skilled workers are getting ready to retire, and they aren't seeing an influx of qualified replacements.
Cliff Thermer, chairman of the Social Science, Business and Education department at Goodwin College in East Hartford and head of its manufacturing program, says the school is trying to entice young people to get interested in the field, while also training adults already looking for work.
"We see an opportunity to prepare the next generation of the workforce," Thermer says, which is why the college created the manufacturing program. "I like to think of us as being part of the solution to the challenges."
Goodwin offers a "certified production technician" class. Though the certification isn't a requirement to hold a manufacturing position, it provides an understanding of the work that makes new applicants more competitive, according to Thermer. Those searching for jobs become attractive to employers with this kind of training, and ideally, the state itself becomes more alluring to outside firms because there is an existing skilled labor force.
"There's a perception issue of what manufacturing is," says Thermer. "When people start seeing this new generation of how things are done and made — it's not your grandfather's old manufacturing. It's very high-tech. When you realize with some background and training, and small investment of your time, that you can break into this industry and have a good-paying job — and I think most people in life want to do something that's significant, they want to do something that matters — manufacturing matters."
Click on any town to see the unemployment rate.
Part of the problem is finding interested applicants who are qualified to fill positions that are open.
Like other educational institutions, Goodwin College has also noticed a huge demand for health care and nursing, and consequently created a robust program to fill those needs and contribute to the skilled workforce.
According to Nancy Steffens, spokesperson for the Connecticut Department of Labor, private institutions are endeavoring to train people to become gainfully employed, and the state is also making an effort to match employers with future employees. The state also works to both help those who are unemployed get jobs by showing them what's available and offering employment tips and resources.
Though there are thousands using the state's online job portal (ctdol.state.ct.us) to find work every day, data on how often jobs are filled as a result of the state's help isn't tracked. Since last August, more than 55,000 jobs have been posted on the site.
Business-service consultants have also counseled employers. "This could include helping them with training programs, matching them up with employees that meet their business requirements, and informing them of tax credits and training incentives," Steffens says.
The Department of Labor also lets businesses know about a subsidized employment and training program that offers grants for hiring an unemployed person. There's also a shared work program where employers "facing tough times" can have employees working fewer hours receive unemployment insurance benefits.
"This helps employers avoid layoffs and allows them to retain their skilled workers," she says. "They are ready to hit the ground running when business picks up."


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Promoting public appreciation of Paralympic athletes with learning disabilities
A new video produced with the help of a public engagement grant from the Society is helping the public understand the classification rules for athletes with intellectual disabilities taking part in the London 2012 Paralympics.
The video features Chartered Psychologist Professor Jan Burns from Canterbury Christ Church University who is the Head of Eligibility for INAS – the International Federation for sport for para-athletes with an intellectual disability. It also includes interviews with athletes and officials involved in the Games.
You can watch the video on this website.
Professor Burns was interviewed about her work on the BBC Radio 4 Today programme last week and was also recently in Nature. In May she and her team at Canterbury Christ Church won an award for their work on the Games, triumphing over 230 other nominated projects.
Photo courtesy of INAS - 2009 half-marathon championships


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Monthly Archives:: October 2010
Flames doused, investigation begins
MOUNT VERNON — The Mount Vernon fire and police departments are partnering with the Division of State Fire Marshal and the Bureau of Alcohol, Tobaco, Firearms and Explosives to investigate the the cause of the fire that gutted a downtown building on Monday.
Downtown businesses start reopening today
MOUNT VERNON — Downtown business owners wanting to know if they should open their doors today in the wake of Monday's tragic fire received a briefing Tuesday morning from Mount Vernon Fire Department Assistant Chief Chris Menapace.
Some city streets closed down for fire
MOUNT VERNON — Although the fire department naturally assumes the lead when a conflagration strikes a city, other service agencies, such as the police, have a strong supporting role.
City discusses proposed rate increase for county jail
MOUNT VERNON — Mount Vernon City Council's Budget and Finance Committee discussed the renewal of the city's contract with the Knox County Jail which expires at the end of the year.
HCA makes plea to City Council
MOUNT VERNON — Members of the Heritage Centre Association and the Greater Downtown Management Council presented a plea to Mount Vernon City Council on Monday night to continue a renewal of the bed tax funds allocated to the HCA and the Mount Vernon Parking Co.
Corn field burns near Fredericktown
FREDERICKTOWN — Hot coals dumped from a grill started a fire in corn stubble Monday, according to Fredericktown firefighters.
Knox giving back to his school
MOUNT VERNON — Maximizing his own potential while helping others, 22-year-old James Knox, confined to a wheelchair due to spina bifida, decided to focus on his abilities and not his disabilities.
Have you done any political work for campaigns this year?
Downtown building a 'total loss'
MOUNT VERNON — A fire that started in the basement of downtown Mount Vernon building will soon result in an empty corner at Main and Gambier streets.
Fire damages downtown building
MOUNT VERNON — A basement fire early this morning at 201 S. Main St. spread throughout the building as firefighters from Knox County fought the blaze.
Students set for graduation tests
MOUNT VERNON — The fall administration of the Ohio Graduation Tests starts today, and while Ohio students have been preparing for the tests for years, guest students from foreign countries have not.
Phillips finishes 3rd in state
COLUMBUS — The third time was finally a charm for Mount Vernon's Charlie Phillips.
Jackets shocked at home, 2-0
MOUNT VERNON — It wasn't supposed to end this way. The Mount Vernon Yellow Jackets boys soccer team fell, and fell hard, Saturday night at home to Reynoldsburg, 2-0, in the Sectional Final.
East Knox soccer loses to top seed
COLUMBUS — The East Knox Bulldogs soccer team ended its best season ever on a note of hope, despite dropping the second round OHSAA Division III tournament match to top-seeded and undefeated Grandview Heights, 6-1, on Saturday afternoon.
Freddies, Trojans have strong showing at cross country Districts
PATASKALA — Both the Fredericktown boys and girls cross country teams, as well as the Centerburg girls, advanced to regional competition after strong days at the districts Saturday.
Lady Jackets have highest finish ever
PATASKALA — For the Mount Vernon girls cross country team, Saturday was a day to celebrate history. For the boys, it was a learning experience with a fun reward for one runner's hard work.
Downtown fire
Discussion closed, new blog entry posted MOUNT VERNON — The Mount Vernon Fire Department is currently responding to a basement fire at 201 S. Main St. The MVFD was dispatched at approximately 6:45 this morning to a call of a basement fire. Bodi N Balance is located on the first floor of the building. South Main… Read more »
2010 Devil Dog Game
game time 7:00 p.m. Saturday, October 30 East Knox High School video Big plays make difference in Devil-Dog game Blue Devils defeat Bulldogs 2009 Devil Dog Game image gallery 2009 Devil Dog Game Blue Devils defeat Bulldogs stories Danville beats East Knox in OT 2006 Big plays make difference in Devil-Dog game 2007 Blue Devils defeat Bulldogs 2008… Read more »
Has the US lost its appetite for big public works projects?
An interactive world map comparing U.S. infrastructure projects with overseas construction has been posted. Has the nation that built the Hoover Dam, brought electricity to the rural South and engineered the interstate highway system lost its appetite for big public works projects? At a time when other countries are pouring money into steel and concrete,… Read more »


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An accident in the right lane of I-610 East has closed off the exit ramp near Canal Boulevard and is causing heavy delays for morning commuters in New Orleans. According to the Louisiana Department of Transportation all lanes of eastbound I-610 are blocked before Canal Boulevard due to a multi-vehicle accident. The accident occurred shortly before 8 a.m. and involved an overturned vehicle in the right lane of I-610 East.
The I-610 East exit ramp is closed with traffic passing on the right shoulder. The New Orleans Police Department said that there were injuries caused by the accident, but that the severity of them was still unknown.
Check back with NOLA.com for more traffic updates.


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Lesson Plan
Chains Discussion Guide
- Grades: 6–8
About this book
Grade Level Equivalent: 4.7
Lexile Measure: 780L
Guided Reading Level: Z
Age: Age 11, Age 12, Age 13
Genre: Historical Fiction, Multicultural
Subject: Colonial and Revolutionary America, American Revolutionary War, Slavery, Underground Railroad, Abolition, African American, Women's History and Experience
Discussion Topics for Chains by Laurie Halse Anderson
- Describe the life of slaves in the American colonies in the 1700s. Discuss the difference between a servant and a slave. How did Miss Mary Finch's view of slavery differ from that of most slave owners? Why does Mr. Robert accuse Isabel of lying when she tells him that she read Miss Mary's will? Explain why Pastor Weeks thinks that teaching a slave to read only "leads to trouble."
- Mr. Robert collects Isabel and Ruth on the day of Miss Mary's funeral. Why aren't the girls allowed to take personal items with them? Explain the symbolism of the seeds that Isabel hides in her pocket. She plants the seeds, and one day finds that the plants have died. What do the dead plants represent? There is another plant metaphor in the novel. Explain what the mayor of New York means when he compares the rebels to vines.
- Role models may be found in real life and in stories. How are Isabel's momma and Queen Esther, from the Bible, her role models for bravery? Discuss the connection between bravery, courage, and fear. What is Isabel's first act of bravery? Discuss her most fearful moments. How is her bravery and courage fueled by her fears? How does she become bolder and braver as the novel develops?
- The American Revolution was about freedom and liberty. Mr. Lockton, a Loyalist, thinks that freedom and liberty has many meanings. Define freedom from his point of view. How might the Patriots define freedom and liberty? Isabel has lived her entire life in bondage, but dreams of freedom. What does freedom look like in Isabel's mind?
- Discuss why Curzon thinks that Isabel will be a good spy. At what point does she accept his offer? Isabel feels betrayed by Curzon. How is Curzon betrayed by Colonel Regan? At what point does Isabel understand that Curzon's dream of freedom is the same as hers? How does this realization help her forgive him? At the beginning of the novel, Isabel needs Curzon. How does he need her at the end of the novel?
- Isabel encounters a woman in the street singing "Yankee Doodle," and realizes that the woman is a messenger. What is the message? Colonel Regan gives Isabel the code word ad astra to use when entering the rebel camp. The word means "to the stars" in Latin. Why is this an appropriate code word for the rebels? How does this word foreshadow Isabel and Curzon's ultimate escape to freedom at the end of the novel?
- The mayor of New York, a Loyalist, says, "The beast has grown too large. If it breaks free of its chains, we are all in danger. We need to cut off its head." Who is the beast? Who is the head? Why is Lockton so adamantly opposed to the mayor's proposal?
- Isabel says, "Madam looked down without seeing me; she looked at me face, my kerchief, my shirt neatly tucked into my skirt, looked at my shoes pinching my feet, looked at my hands that were stronger than hers. She did not look into my eyes, did not see the lion inside. She did not see the me of me, the Isabel." What is the lion inside of Isabel? What does Lady Seymour see in Isabel that Madam Lockton doesn't see? How does the "lamb" in Lady Seymour help the "lion" inside of Isabel escape?
- Explain the following metaphor: "Melancholy held me hostage, and the bees built a hive of sadness in my soul." What precipitates such sadness in Isabel? How does the hive grow bigger before Isabel learns to destroy it?
- The old man that Isabel calls Grandfather says, "Everything that stands between you and freedom is the river Jordan." He assures her that she will find it if she looks hard enough. What is the figurative river Jordan in the novel? Discuss all of the tributaries that feed into Isabel's river Jordan.
- The bookseller gives Isabel a copy of Common Sense by Thomas Paine. He advises her that the words are dangerous, and that she should commit them to memory. At what point does she understand Paine's words? How does the book give her courage?
- What does Isabel mean when she says, "I was chained between two nations"? There are several references to chains throughout the novel. How is the word "chain" used as an antonym to the word "freedom"?
This guide is provided by Simon & Schuster for library, classroom, and reading group use. It may be reproduced for these purposes.
- Subjects:Colonial and Revolutionary America, American Revolutionary War, Slavery, Underground Railroad, Abolition, Literary Criticism and Analysis, Story Elements, Reading Response, African American, Social Studies through Literature, Women's History and Experience
- Skills:Literary Elements, Reading Comprehension, Listening Comprehension
Dec 31, 1969


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Ah the tragedies of being a PC owner in a gaming world increasingly dominated by game consoles. Now it seems, not only is Need For Speed: Hot Pursuit's first downloadable content a console exclusive, the PC won't be getting any of the planned console DLC.
A post by one of the developers in the official EA Need for Speed forums under the name EASpenser explains Criterion's postition:
Hey all, unfortunately we will not be releasing Need for Speed Hot Pursuit PDLC for the PC. While we are certainly committed to providing the best possible game experience and ongoing support for our PC community, (as you have already noted) we have a limited amount of resources that makes it so that we are unable to deliver new content to all platforms. We sincerely apologize for any inconvenience, but on the positive side we do have more updates and content on the way for PC players–look for news very soon.
If I played Need for Speed on the PC I wouldn't be completely discouraged, as the statement seems to hint that the PC will receive DLC of it's own.


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A 33-year-old woman, from Overland Park, who suffered a life-changing stroke a couple of years ago recently had a haircut -- so she could make a donation to Locks of Love, which makes hairpieces for ill children.
The views expressed are not those of this site, this station or its affiliated companies. By posting your comments you agree to accept our terms of use. KCCI offers readers the ability to comment on stories with the understanding that these comments may be reprinted elsewhere on the site or used on KCCI newscasts. We ask that you refrain from profanity, hate speech, comments that don't relate to the story and any personal remarks. THIS IS IMPORTANT: KCCI does not edit user submitted statements and we cannot promise that readers will not, at times, find offensive or inaccurate comments posted in this area. If you find a comment that is objectionable or offensive, click the flag that appears in the upper right corner when you hover over a comment. Flagged comments may be automatically hidden from comment threads. For comments to appear on the website and/or the mobile app, email addresses must be verified through Disqus. We ask the community to monitor this forum with the knowledge that KCCI does not regularly monitor these comments.blog comments powered by Disqus


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quote daemon765023just for your information $0.35 per HP is not exactly the acceptable going rate at the moment. At least $0.40 if not $0.50 per HP is the desirable price conversion rate. As they are now it's around $12 already at $0.40 rate, which is usually what I go for, but as Holy War is coming near, and on top of that I might end up building a 6-10 out of them, I will not simply let it go at just a little more than $10 a piece, I'm sorry if that seems unfair to you but I do not find price matching the value of the card.hp=$0.35, in game they are around 30 hp 0.35*30=$10.50 who ever is not paying this price is over paying. ppl please take a look at what they are worth in game and then price it on what the going exchange rate for hp then pay that price!!!
quote SpiesundercoverSorry no more hpAnymore hp? Email me


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THERE'S still a long way to go in terms of league climbing for Selkirk FC – but with two wins in their last two outings, coaching staff are beginning to see a glimmer of light at the end of the tunnel.
Tomorrow the team face Berwick Rangers Reserves, who are fourth in the table, in a home encounter at Yarrow Park – and coach Aaron Biggs is looking for the hat-trick.
"We drew with Berwick in the League Cup at the start of the season and they are a very useful side," he told The Wee Paper earlier this week, adding: "I am expecting it to be another close game on Saturday, but having won our last two games our confidence has risen, so here's hoping we can make it three in a row."
Euan Pritchard is still on the injury list, but apart from that the team are fighting fit.
Last weekend Selkirk came out top in a Division One derby dogfight against an ever-improving Hawick Royal Albert, and after a slow start the Souters managed to raise their game to take a comfortable 3-1 victory.
Although the action was low key, Selkirk always looked the more dangerous in the early stages of the game, with David Battle and Jonny Watt both going close. Skipper John Dodds was also in his usual good form and managed to keep a firm hold on the few shots that did come his way.
Selkirk broke the deadlock in the 39th minute when Barry Milven latched onto a well-executed corner kick to head the ball into the net.
Hawick equalised on the hour, Steven Allan slotting away a penalty after Bobby Nwanze was deemed to have been pushed by Kenny Munro – but the rest of the game belonged to Selkirk. Michael Holness and Watt added another two goals to secure a much-needed victory.
Looking back on the game, Biggs commented: "I was not exactly delighted with our footballing show, but I sure was delighted with the result."
He added: "We rode our luck at times, but I was pleased with the attitude and character we showed throughout the match and this was a big turnaround from what it was like three or four weeks ago."


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The following is a sample of calls received by the central dispatch office for Quay County, based at the Tucumcari Police Department, during the last few days. According to reports:
At 1:45 p.m., a female came to the police department regarding some stolen Department of Labor checks.
At 1:41 a.m., a female reported that juveniles were breaking windows.
An officer advised that juveniles had broken a 3 foot by 1 foot window in a residence across the street from the caller.
At 2:49 a.m., a female called for an officer at a convenience store on First Street because an intoxicated female was trying to get in her car and drive away. The caller advised she'd taken the subject's car keys. An officer advised that he had taken the subject home.
At 9:59 a.m., a male called to report that a bike has been thrown into the trees at a South Jackson residence. Officer advised that a X-Games Scooter had been logged into found property and stored.
At 5:23 p.m., a female reported a stolen vehicle. The officer advised that the a four-wheeler had been stolen from a South 10th Street residence.
At 8:39 p.m., a male called about a possible fight on South Fourth Street. An officer advised that a juvenile was arguing with her mother about going somewhere with her. The officer spoke with both mother and child; and the juvenile went with the her mother.
At 9:57 p.m., multiple calls were made regarding a dumpster fire at the shooting range at Five Mile Park. Firefighters were dispatched to the fire.
At 11:53 p.m., a female reported a suspicious vehicle in an alley on South Sixth Street. The officer patrolled the area and did not find a suspicious truck.
At 12:55 p.m., a female called about a suspected shoplifting of a 20-ounce soda by a male wearing a baseball cap and carrying a backpack at a convenience store on First Street. An officer reported that the subject bought a Coke at the hospital from the machines and his story was collaborated by the amount of money he still had.


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tag:blogger.com,1999:blog-2007702193183659560.post1569621956227884579..comments2016-09-10T18:13:43.172-04:00Comments on Miami Heat Index: Timberwolves' Bane: With LeBron James On Point, James Jones and the Miami Heat Shoot Down Minnesota 129-97reservoirgodhttp://firstname.lastname@example.com:blogger.com,1999:blog-2007702193183659560.post-1757187870004914332010-11-05T10:52:46.454-04:002010-11-05T10:52:46.454-04:00Shawn: Glad you liked the game recaps. I'm op...Shawn:

Glad you liked the game recaps. I'm open to suggestions for improvement, so if you have any then please leave them in the comments. This is definitely a work in progress.reservoirgodhttp://firstname.lastname@example.com:blogger.com,1999:blog-2007702193183659560.post-89424965559218038972010-11-04T12:02:04.076-04:002010-11-04T12:02:04.076-04:00It's taken me a while to get around to reading...It's taken me a while to get around to reading this blog, I read the first couple posts but then got behind...

Anyway, I really like your game recaps. The quarter by quarter EWP48 is great as well as your description of pivotal turns. The only Heat game I've caught so far was against the Celts on opening, which was pretty underwhelming, as you know. Looks like I've been missing out though.Shawn Ryanhttp://email@example.com


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Limited Edition Bulldog T-Shirt - Unisex
The first of our Limited Edition T-Shirts features the Bulldog. Our Limited Edition Ts will be available for a short time before the design goes into the vault. You never know when these cool designs will be re-released, so it's best to get it when you see it! These fun designs feature different breeds of dogs, unisex fit is perfect for men or women.
100% ringspun cotton.
Taped shoulder-to-shoulder.
Preshrunk, soft-washed, garment-dyed fabric.


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Begin Your Search
WineAccess Travel Log
Read stories from the world's greatest wine trails.
More About This Wine
Related Products
Additional Vintages
Other Wines from this Producer and Vintage
2010 Domaine Gilbert Picq et Ses Fils Chablis Vosgros
Producer: Domaine Gilbert Picq et Ses Fils
Style: White Wine
Grape Type: Chardonnay
Origin: France
Region: Burgundy
Appellation: Chablis
93 Points | Stephen Tanzer's IWC - July/August 2012
(bottled in February of 2012): Pale straw-yellow. Sexy, explosive aromas of powdered stone, orange peel and toasted biscuit. Then much more closed in the mouth, showing superb concentration and tension to the firm flavors of crystallized lime, peach and salty minerals. Really exceptional energy and verve here. The mineral-driven finish offers an uncanny combination of salinity and sucrosite. This wine possesses the sheer density of material to improve in bottle for 15 to 20 years.


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Welcome to the new Educational Accents website. We carry a good many titles of Pathway Publishers homeschool textbooks. As they are all used, you
will save a good deal of money. Please feel free to search our website for these books. You'll see the beginning our Pathway Publishers Search listed below on this page.


text: Enjoy an Extra 15% off Shoes, Apparel, and Fine Jewelry with Sears promo code: SEARSMAR. Offer applies to items sold by Sears and in the cart. Offer not valid during Friends & Family events. Excludes Powered by Shoebuy, Levi's, Lee, Haggar, Mac's, All Watches, Clearance, Great Price Shoes, and Great Price Jewelry.


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Solution allows consumer research without leaving financial institution's website.
Company reports 2 million product impressions for credit union and bank clients.
NASHVILLE, Tenn. — Two educational breakout sessions at NAFCU's annual conference provided ideas to produce fee income that also increase membership value.
The practice of selling insurance has changed, according to Insuritas President/CEO.
What might look like a typical thumb drive to members of Northern Lights Federal Credit Union may actually be what regulators consider a top-tier secure and compliant way to access the Internet for online banking and shopping.
Security firm offers to replace millions of tokens, implement new measures aimed at protecting Web-based financial transactions.


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Here are a few social or entertainment-related events in Hoboken occurring tonight and tomorrow, so you plan your weekend right:
- Tonight there's a comedy show at the Monroe Arts Center, 720 Monroe St. Nate Bargatze, a comedian who has appeared on Late Night with Conan O'Brien, Live at Gotham and at the Just for Laughs Montreal Comedy Festival in the 'New Faces' category. VH1's Pat O'Shea hosts and comedienne Liz Miele opens for Bargatze. Tickets are $15, the show starts at 9 and parking is free. The event's BYOB.
- Fuzzy Lemons, a New Jersey family-friendly rock band, are playing tomorrow at 11:15 a.m. and 4 p.m at Monroe Theatre Space. Each show costs $5.
- New Jersey Young Professionals is throwing an anniversary party for itself, celebrating its past six years. The party's going down tonight at Room 84, 84 Washington St., from 7 to 9 p.m. The organization's success stories – those married or with kids who met at their events – are encouraged to attend. Non-members pay $20 online or at the door, and members' cover charge is determined by how many have pre-registered thus far. The specials are $5 house wines and champagne, $5 well drinks and $3 tap beers.


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Do all you little Edgesters remember what you learned about The Pantheon, that building in Rome, commissioned by Marcus Agrippa as a temple to all the gods of Ancient Rome, and rebuilt by Emperor Hadrian?
Well, we aren't gonna bore you with that ancient history stuff. Nah, we are totally up to date with our humor columns. Check this out:
The Modern-Day Pantheon
Zeus, god of illegal fireworks, blimps, and pun-driven ad campaigns.
Hera, goddess of anyone who has stood on a street corner with a sign that begins HONK IF YOU LOVE ______.
Poseidon, god of inflatable baby pools and books for girls who love horses.
Demeter, goddess of organic vegetables, inorganic vegetables, and those plastic vegetables you find in the grocery store exhibit at a children's museum.
Hestia, goddess of exposed brick interior walls.
Apollo, god of people who string up Christmas lights professionally, kazoos, and high school literary magazines.
Aphrodite, goddess of speed dating, America's Next Top Model catch-phrases, and laser hair-removal Groupons.
Hermes, god of places that accept American Express.
Artemis, goddess of Craigslist, word search puzzles, and those raccoons living in your crawl space that you once called 9-1-1 on because you thought you "heard footsteps."
Dionysus, god of Franzia and body glitter.
Athena, goddess of adult kickball leagues, people who have been reading Infinite Jest for the past 10 months and are only on page 132, and Ric Rac.
Ares, god of kids who make it past their yellow belts in after-school karate.
Hades, god of pterodactyls, the old food pyramid, and AOL chat rooms, may they rest in peace.


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Hilton Chicago/Indian Lakes Resort250 W. Schick Road, Bloomingdale, Illinois, 60108, USA TEL: +1-630-529-0200 FAX: +1-630-529-9271
Hilton Chicago/Indian Lakes Resort, Bloomingdale, IL - Resolution Spa & Wellness Center
Resolution Spa Package
Our Chicago-area resort has it all, including five restaurants and bars, a full-service spa and wellness center, an indoor and outdoor pool, and a fitness center. Take a break from the daily grind and plan a night out with the girls at our Hilton Chicago/Indian Lakes resort now.
The Resolution Spa package includes:
- Overnight accommodations for up to 4 Guests
- One of the following: 60-minute Swedish massage, Rejuvenating Marine facial, or a Resolution Spa Manicure and Pedicure
- Breakfast Buffet at Masters Grill
- One complimentary beverage at the Cave Bar, located in our resort
All rates are subject to hotel availability; rate does not include taxes, gratuities or other incidental charges; certain length of stay restrictions may apply. Early departure fee may apply. This offer may not be combined with any other discounts or offers. If you are not interested in making this reservation online, please call our Internet Customer Center at 1-800-774-1500 or click here for a complete list of Hilton Reservations Worldwide phone numbers. Please request plan code "P4".


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If you have a broken heating or cooling system in Denver, HVAC repair from TOBIN Heating & Air Conditioning is just a phone call away.
In business since 1954, TOBIN has been serving Denver HVAC needs for over 58 years! All of our technicians are clean-cut, uniformed and licensed. We provide to both residential and commercial customers' needs for repairs, preventive maintenance, and installation. Coupled with exceptional customer service and quality that'll exceed your expectations, TOBIN is the best price in town on Denver HVAC. Call TOBIN Heating & Air Conditioning at 303-893-5675 for affordable cost estimates on repairs to your Denver HVAC systems. We also do FREE estimates on any installation project, including venting and ductwork. Check out TOBIN's A+ rating and Gold Star Award status with the BBB.
We are licensed and insured, and always showing our customers they are in safe hands working with us. We offer a one-year workmanship warranty on equipment replacements and installations and offer extended warranties for up to ten years on systems we install. We accept all major credit cards and have financing available to make sure our customers get the best service no matter what means they need to pay by. Don't wait to get the problem fixed; contact TOBIN today to get us working on your HVAC system ASAP.
We are very involved in the community and have worked wonderfully with our friends and neighbors across the Denver Metropolitan area since 1954. Turn to the people who everyone trusts with a phone call to TOBIN – we look forward to exceeding your expectations with the fantastic work that we do.


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of Lena
Charles Theodore and Augusta Dalluge Weise/Wise
This story is contained in the book "Trial and Trumph on a Western Frontier - thrilling stories of Adventist Pioneering" by Adriel D. Chilson. Story starts on page 166:
"In the community of Couillardville, southwest of Oconto, Mr. and Mrs. Charles Wise were tenant laborers on the Ritter Ranch. When Elders Bourdeau and Loughborough held a series of meetings in Oconto, the Wise family attended. Although his wife accepted, Charles was not fully decided. One night soon after retiring, Mrs. Wise had a firightening dream from which she soon awakened and told her husband. "I dreamed we were out working in the field. The sky became dark, and a strange funnel-shaped cloud appeared. Then, an angel spoke to me, 'take your family and go to a rise of ground yonder, and there you will be safe. Flee with just your family and the clothes you have on.' We did as directed and the storm became so black we could not see anything. I heard a very loud crash, then awakened, happy to find myself in my own bed." Charles told her to forget the dream and stop worrying, but it had made a deep impression, and she related it again at the breakfast table. Mr. Ritter was not a bit understanding, and remarked to Charles, "Her new religion, and now this dream. I think your wife needs to be put away." July 7, 1877 was a hot, humid Saturday. An afternoon thunderstorm was approaching from the southwest, but work went on as usual. Then, a second storm came from a more northerly angle, traveling on a collision course with the first one. Darkness signaled the cows from the pasture, so Charles began the evening chores. Mrs. Wise explained to her husband that this was the storm of her dream. He just smiled and told her to find shelter if she wished but he would continue with the milking. Her older son, William stayed behind to help. Taking with her Etta, Herman, and the baby Theodore, Mother Wise hurried to the place of refuge. She thought of a package of bright-colored cloth she had just purchased to make a dress. But no, she would not return to the house. She remembered the instructions - "flee with just your family and the clothes you have on." She looked toward the barn in time to see William picked up by the wind and carried a hundred feet in her direction. Her husband was running toward him. Soon, all reached the spot to which she had been directed in the dream, an uprooted stump surrounded by alder brush. Here they huddled and prayed. The fury of the storm snatched some of the clothing from their backs. When it passed, they returned to where the farm buildings had stood. They were totally demolished. The cow Mr. Wise had been milking was blown against the pump and killed. Mr. Ritter was found in a creek bed a mile away suffering a broken hip from which he never recovered. Mrs. Wise could not locate the package of material for her new dress, but among the possessions scattered over the yard was an earthern butter jar she had brought from Germany, now prized by her granddaughter, Hazel Niquette. "Truly your dream was sent by the Lord, and we are spared," her husband observed. Charles soon joined her in the Adventist faith and became a colporteur-evangelist. The storm from which they were saved is known in history as the Pensaukee Tornado because of the near total destruction it caused in this bayshore community."
Wise Family of Lena, Oconto County, Wisconsin
c: 1920
Augusta Dalluge Wise is seated front left and her husband Charles Theodore Wise is seated front right.
Second row seated left to right:
Charles F. Wise, Cereda Little Wise (Charles F.), Mary Rydell Wise (John).
Third row standing left to right:
Henrietta Wise Feak, William Wise, Emma Fenske Wise (William) Herman Wise, John Wise, Louisa Kottke Wise (Herman)