A second generation radiation hybrid map to aid the assembly of the bovine genome sequence

BACKGROUND: Several approaches can be used to determine the order of loci on chromosomes and hence develop maps of the genome. However, all mapping approaches are prone to errors either arising from technical deficiencies or lack of statistical support to distinguish between alternative orders of loci. The accuracy of the genome maps could be improved, in principle, if information from different sources was combined to produce integrated maps. The publicly available bovine genomic sequence assembly with 6x coverage (Btau_2.0) is based on whole genome shotgun sequence data and limited mapping data however, it is recognised that this assembly is a draft that contains errors. Correcting the sequence assembly requires extensive additional mapping information to improve the reliability of the ordering of sequence scaffolds on chromosomes. The radiation hybrid (RH) map described here has been contributed to the international sequencing project to aid this process. RESULTS: An RH map for the 30 bovine chromosomes is presented. The map was built using the Roslin 3000-rad RH panel (BovGen RH map) and contains 3966 markers including 2473 new loci in addition to 262 amplified fragment-length polymorphisms (AFLP) and 1231 markers previously published with the first generation RH map. Sequences of the mapped loci were aligned with published bovine genome maps to identify inconsistencies. In addition to differences in the order of loci, several cases were observed where the chromosomal assignment of loci differed between maps. All the chromosome maps were aligned with the current 6x bovine assembly (Btau_2.0) and 2898 loci were unambiguously located in the bovine sequence. The order of loci on the RH map for BTA 5, 7, 16, 22, 25 and 29 differed substantially from the assembled bovine sequence. From the 2898 loci unambiguously identified in the bovine sequence assembly, 131 mapped to different chromosomes in the BovGen RH map. CONCLUSION: Alignment of the BovGen RH map with other published RH and genetic maps showed higher consistency in marker order and chromosome assignment than with the current 6x sequence assembly. This suggests that the bovine sequence assembly could be significantly improved by incorporating additional independent mapping information.

Alcohol dehydrogenase 1C*1 allele is a genetic marker for alcohol-associated cancer in heavy drinkers

Chronic alcohol consumption is associated with an increased risk for upper aerodigestive tract cancer and hepatocellular carcinoma. Increased acetaldehyde production via alcohol dehydrogenase (ADH) has been implicated in the pathogenesis. The allele ADH1C*1 of ADH1C encodes for an enzyme with a high capacity to generate acetaldehyde. So far, the association between the ADH1C*1 allele and alcohol-related cancers among heavy drinkers is controversial. ADH1C genotypes were determined by polymerase chain reaction and restriction fragment length polymorphism in a total of 818 patients with alcohol-associated esophageal (n=123), head and neck (n=84) and hepatocellular cancer (n=86) as well as in patients with alcoholic pancreatitis (n=117), alcoholic liver cirrhosis (n=217), combined liver cirrhosis and pancreatitis (n=17) and in alcoholics without gastrointestinal organ damage (n=174). The ADH1C*1 allele and genotype ADH1C*1/1 were significantly more frequent in patients with alcohol-related cancers than that in individuals with nonmalignant alcohol-related organ damage. Using multivariate analysis, ADH1C*1 allele frequency and rate of homozygosity were significantly associated with an increased risk for alcohol-related cancers (p<0.001 in all instances). The odds ratio for genotype ADH1C*1/1 regarding the development of esophageal, hepatocellular and head and neck cancer were 2.93 (CI, 1.84-4.67), 3.56 (CI, 1.33-9.53) and 2.2 (CI, 1.11-4.36), respectively. The data identify genotype ADH1C*1/1 as an independent risk factor for the development of alcohol-associated tumors among heavy drinkers, indicating a genetic predisposition of individuals carrying this genotype.

Dysferlin is a new marker for leaky brain blood vessels in multiple sclerosis

Dysferlin is a muscle protein involved in cell membrane repair and its deficiency is associated with muscular dystrophy. We describe that dysferlin is also expressed in leaky endothelial cells. In the normal central nervous system (CNS), dysferlin is only present in endothelial cells of circumventricular organs. In the inflamed CNS of patients with multiple sclerosis (MS) or in animals with experimental autoimmune encephalomyelitis, dysferlin reactivity is induced in endothelial cells and the expression is associated with vascular leakage of serum proteins. In MS, dysferlin expression in endothelial cells is not restricted to vessels with inflammatory cuffs but is also present in noninflamed vessels. In addition, many blood vessels with perivascular inflammatory infiltrates lack dysferlin expression in inactive lesions or in the normal-appearing white matter. In vitro, dysferlin can be induced in endothelial cells by stimulation with tumor necrosis factor-alpha. Hence, dysferlin is not only a marker for leaky brain vessels, but also reveals dissociation of perivascular inflammatory infiltrates and blood-brain barrier disturbance in multiple sclerosis.

EmsB, a tandem repeated multi-loci microsatellite, new tool to investigate the genetic diversity of Echinococcus multilocularis

In order to explore the genetic diversity within Echinococcus multilocularis (E. multilocularis), the cestode responsible for the alveolar echinococcosis (AE) in humans, a microsatellite, composed of (CA) and (GA) repeats and designated EmsB, was isolated and characterized in view of its nature and potential field application. PCR-amplification with specific primers exhibited a high degree of size polymorphism between E. multilocularis and Echinococcus granulosus sheep (G1) and camel (G6) strains. Fluorescent-PCR was subsequently performed on a panel of E. multilocularis isolates to assess intra-species polymorphism level. EmsB provided a multi-peak profile, characterized by tandemly repeated microsatellite sequences in the E. multilocularis genome. This "repetition of repeats" feature provided to EmsB a high discriminatory power in that eight clusters, supported by bootstrap p-values larger than 95%, could be defined among the tested E. multilocularis samples. We were able to differentiate not only the Alaskan from the European samples, but also to detect different European isolate clusters. In total, 25 genotypes were defined within 37 E. multilocularis samples. Despite its complexity, this tandem repeated multi-loci microsatellite possesses the three important features for a molecular marker, i.e. sensitivity, repetitiveness and discriminatory power. It will permit assessing the genetic polymorphism of E. multilocularis and to investigate its spatial distribution in detail.

Panel 2: Rescue and Escape from the Holocaust

Panel 2: Rescue and Escape from the Holocaust Nina Paulovicova, University of Alberta, Canada: “The Silenced Phenomenon of Cross-National Rescue: 'Leaking Border' and Paid Smugglers” Download Paper (login required) Tomasz Frydel, University of Toronto: "Rescue or Denunciation of Jews? A Case Study of Southeastern Poland during German Occupation" Download Paper (login required) Tanja von Fransecky, Technical University, Berlin, Germany: "Escape and Attempted Escape of Jewish Deportees from Deportation Trains in France, Belgium and the Netherlands” Download Paper (login required) Chair: Adara Goldberg and Elizabeth Anthony, Clark UniversityComment: Deborah Dwork, Clark University

Panel 3: Encounters of Perpetrators and Victims of Genocides

Panel 3: Encounters of Perpetrators and Victims of Genocides Lina Nikou, University of Hamburg, Germany: “Coming Back Home? Berlin Presents Itself to Refugees of the Nazi Regime Living Abroad” Download paper (login required) Michelle Bellino, Harvard University: “Whose Past, Whose Present? Historical Memory among the ‘Postwar’ Generation in Guatemala” Download paper (login required) Srdjan Radovic, Belgrade University/Institute of Ethnography SASA, Serbia: “Memory Culture, Politics of Place, and Social Actors in the Remembrance of Belgrade's World War II Camp” Download paper (login required) Chair: Michael Nolte and Michael Geheran, Clark University Comment: Omer Bartov, Brown University

Panel 5: Memories and Fantasies of Genocides

Panel 5: Memories and Fantasies of Genocides Mark Hobbs, University of Winchester, United Kingdom: "Destroying Memory: The Attack on Holocaust Conscience and Memory in Britain 1942-2011" Download paper (login required) Kristen Dyck, Washington State University: "Hate Rock: White-Power Music in International Perspective" Download paper (login required) Audrey Mallet, Concordia University, Canada: “The Old Jewish Strangler and Other Ghost Stories: Poles’ Struggle to Come to Terms with the Holocaust” Download paper (login required) Tea Rozman-Clark, University of Nova Gorica, Slovenia: “Oral History: UN Peacekeepers and Local Population of the UN Safe Area Srebrenica” Download paper (login required) Chair: Kimberly Partee and Kathrin Haurand, Clark UniversityComment: Cecilie Felicia Stokholm Banke, Danish Institute for International Studies, Copenhagen

Panel 8: Perpetrators and “Bystanders” of the Holocaust

Panel 8: Perpetrators and “Bystanders” of the Holocaust Rachel Century, University of London, United Kingdom: "Secretaries, Secrets and Genocide: Evidence from the Post-war Investigations of the Female Secretaries of the RSHA” Download paper (login required) Istvan Pal Adam, Bristol University, United Kingdom: "Bystanders to Genocide? The Role of Building Managers in the Hungarian Holocaust" Download paper (login required) Antonio Munoz, St. John's University: “Murderers in Field Grey: Crimes of the Wehrmacht in the Region of the Army Group South, 1941-1942” Download paper (login required) David Deutsch, Ben-Gurion University, Israel: "Goebbels Close Enemies: Intimacy as an Analytic Tool for the Understanding of Genocidal Rhetoric in Goebbels Diaries" Download paper (login required) Chair:Stefan Ionescu and Hannah Schmidt Hollaender, Clark University Comment: Thomas Kühne, Clark University

Panel 9: Aftereffects and Memory of the Holocaust

Panel 9: Aftereffects and Memory of the Holocaust Stefanie Rauch, University of Leicester, United Kingdom: “British Responses to the Film ‘The Boy in the Striped Pajamas’” Download paper (login required) Emily Stiles, University of Winchester, United Kingdom: "The Evil They Helped to Defeat: Exhibiting the Holocaust in Britain's National Museum of Modern Conflict" Download paper (login required) Kara Critchell, University of Winchester, United Kingdom: “The Heart of Holocaust Education: Holocaust Survivors and the Construction of Holocaust Consciousness in Britain" Download paper (login required) Noemi Staszewski, University of Frankfurt, Germany: "The Drama of Getting Dependent on Assistance in the Shadow of the Shoah: Working Experiences with Old Age Survivors in Germany " Download paper (login required) Chair: Emily Dabney and James Burnham Sedgwick, Clark UniversityComment: Marianne Hirsch, Columbia University

Panel 7: Survival Strategies

Panel 7: Survival Strategies Moriya Rachmani, Ben-Gurion University, Israel: “Rituals in Concentration and Extermination Camps and Near Death Situations: Existence, Order, Identity” Download paper (login required) Barbara Hutzelmann, Ludwig-Maximilians University, Germany: “‘I Didn’t Want to Die.’ Jewish Children’s Strategies of Survival in Slovakia: Chances and Limitations" Download paper (login required) Liviu Carare, The Romanian Academy “George Bariţiu” Institute of History, Cluj-Napoca, Romania: "Jews of Czernowitz (1941-1942): Murder, Ghettoization and Deportation" Download paper (login required) Chair: Alexis Herr and Adara Goldberg, Clark UniversityComment: Johannes Lang, Danish Institute for International Studies, Copenhagen

Panel 4: Transnational Memory of Mass Violence

Panel 4: Transnational Memory of Mass Violence Anne Waehrens, University of Copenhagen/Danish Institute for International Studies, Denmark: “Is There a Shared European memory? Holocaust Remembrance in the European Parliament after 1989" Download paper (login required) Ran Zwigenberg, City University of New York: “The Hiroshima-Auschwitz Peace March and the Globalization of Victimhood” Download paper (login required) Mark Zaurov, University of Hamburg, Germany: "The Current Situation of Human Rights for Deaf People with Respect to the Deaf Holocaust" Download paper (login required) Chair: Natalya Lazar and Jody Manning, Clark UniversityComment: Ken McLean, Clark University

Decreasing gut wall glucose as an early marker of impaired intestinal perfusion

OBJECTIVE: The aim of this study was to assess the microcirculatory and metabolic consequences of reduced mesenteric blood flow. DESIGN: Prospective, controlled animal study. SETTING: The surgical research unit of a university hospital. SUBJECTS: A total of 13 anesthetized and mechanically ventilated pigs. INTERVENTIONS: Pigs were subjected to stepwise mesenteric blood flow reduction (15% in each step, n = 8) or served as controls (n = 5). Superior mesenteric arterial blood flow was measured with ultrasonic transit time flowmetry, and mucosal and muscularis microcirculatory perfusion in the small bowel were each measured with three laser Doppler flow probes. Small-bowel intramucosal Pco2 was measured by tonometry, and glucose, lactate (L), and pyruvate (P) were measured by microdialysis. MEASUREMENTS AND MAIN RESULTS: In control animals, superior mesenteric arterial blood flow, mucosal microcirculatory blood flow, intramucosal Pco2, and the lactate/pyruvate ratio remained unchanged. In both groups, mucosal blood flow was better preserved than muscularis blood flow. During stepwise mesenteric blood flow reduction, heterogeneous microcirculatory blood flow remained a prominent feature (coefficient of variation, approximately 45%). A 30% flow reduction from baseline was associated with a decrease in microdialysis glucose concentration from 2.37 (2.10-2.70) mmol/L to 0.57 (0.22-1.60) mmol/L (p < .05). After 75% flow reduction, the microdialysis lactate/pyruvate ratio increased from 8.6 (8.0-14.1) to 27.6 (15.5-37.4, p < .05), and arterial-intramucosal Pco2 gradients increased from 1.3 (0.4-3.5) kPa to 10.8 (8.0-16.0) kPa (p < .05). CONCLUSIONS: Blood flow redistribution and heterogeneous microcirculatory perfusion can explain apparently maintained regional oxidative metabolism during mesenteric hypoperfusion, despite local signs of anaerobic metabolism. Early decreasing glucose concentrations suggest that substrate supply may become crucial before oxygen consumption decreases.