mercredi 25 juin 2008
mardi 24 juin 2008
Böse Araber, böse Deutsche
Amerikas Kino liebt es, Feindbilder zu produzieren.
Das sagt der neue Antiheld der TV-Serie »24«, Alexander Siddig
ZEIT ONLINE 26/2008 S. 46 [http://www.zeit.de/2008/26/Interview-Siddig]
Die amerikanische Fernsehserie 24 beschreibt wie keine andere das ambivalente, aus Angst und Aggression gemischte Lebensgefühl der Amerikaner nach dem 11. September: Der Agent Jack Bauer (Kiefer Sutherland), angestellt bei einer fiktiven »Counter Terrorist Unit«, jagt Verschwörer, Terroristen und alle Feinde der Vereinigten Staaten – am liebsten Araber. Hat er die gefasst, foltert er sie, bis sie die Wahrheit preisgeben über eine tickende Bombe oder einen geplanten Atomschlag. Notfalls droht er, ihre Kinder zu ermorden, und rettet so sein Land. Mit dieser Entschlossenheit wurde Jack Bauer in den USA populär, sodass sich bereits republikanische Präsidentschaftskandidaten mit ihm verglichen. Auch bei den US-Soldaten im Irak und in Afghanistan ist die Serie beliebt, und der Chef des Office of Homeland Security ist natürlich Fan. In den USA läuft 24 auf Fox; jede Staffel entspricht einem Tag, jede Folge einer Stunde. In Deutschland lief die Serie bisher auf RTL2, die sechste Staffel beginnt am 23. Juni nun auf ProSieben – mit dem sudanesisch-britischen Schauspieler Alexander Siddig als arabischem Bösewicht.
DIE ZEIT: Herr Siddig, was hat Sie an der Rolle des Hamri Al-Assad interessiert, eines islamischen Terroristen, der im ersten Golfkrieg gegen die USA kämpfte?
Alexander Siddig: Die Figur wirkt zunächst böse, könnte aber auch gut sein. Erst will Hamri Al-Assad bloß Rache, dann paktiert er mit dem amerikanischen Präsidenten, um Frieden zu bewirken. Im Grunde ist er ein Idealist, der Mörder war.
ZEIT: Sein Gegenspieler Jack Bauer foltert gern. Mit diesem reißerischen Konzept haben die Produzenten von 24 gigantische Gewinne gemacht. In den USA wird gerade die siebte Staffel gedreht.
Siddig: Der Grund für den Erfolg ist aber Kiefer Sutherland, der die Hauptrolle spielt, ein großartiger Kollege. Wenn dem der Dialog nicht passt, dann ändert er einfach das Drehbuch. Ich habe das auch versucht, leider nicht so erfolgreich.
ZEIT:24 stilisiert Araber zu Buhmännern. Kennen Sie Jack Shaheens Buch Real Bad Arabs? Darin heißt es, Hollywood stelle Araber seit dem Zweiten Weltkrieg nur noch als böse dar – genau wie Indianer, Schwarze und Japaner.
Siddig: Na ja, vor einer Weile galten Araber als romantisch, denken Sie an Omar Sharif. Mit 9/11gab es eine dramatische Wende, als wir plötzlich zu ganz gefährlichen Leuten wurden. Aber mir persönlich hat das nie viel Ärger bereitet. Wer wird denn von Hollywood nicht negativ stereotypisiert? Auch die Briten und die Deutschen sind immer die Bösen.
ZEIT: Immerhin haben Sie mal beklagt, dass Sie nur noch Rollen als Araber bekämen.
Siddig: Ich habe in The Hamburg Cell Chalid Scheich Mohammed gespielt, den Chefplaner von 9/11. Das hat meine Karriere in Wahrheit befördert. Ich bekam Charakterrollen in Ridley Scotts Kingdom of Heaven, wo es um die Kreuzzüge geht, und in Syriana, wo ich den Prinzen eines arabischen Emirats spielte. Diese Filme wären ohne 9/11 gar nicht geschrieben worden.
ZEIT: Der Prinz endet allerdings tragisch: Er und seine Familie werden von der CIA umgebracht.
Siddig: Ja, aber es war immerhin ein muslimischer Charakter, der ein Herz hatte und der die arabische Welt verbessern wollte. Das sehen wir selten. Und das Timing für den Film war perfekt. Als der auf die Leinwand kam, hatten viele Amerikaner fast vergessen, dass es solche Menschen überhaupt gibt. Stattdessen hatten sie nur wütende Mobs vor den Augen, die vor den TV-Kameras Selbstmordattentate ankündigten. Unser Film hat gezeigt, dass Araber auch Menschen sind.
ZEIT: Das Interessanteste an Syriana waren allerdings amerikanische Secret-Service-Agenten, die insgeheim alles per Fernsteuerung kontrollieren.
Siddig: Ja, und ich habe das Gefühl, so ähnlich ist es auch im Irak. Dabei bin ich mir immer noch nicht sicher, was das Motiv für den Krieg war. Öl, natürlich, aber vielleicht geht es noch um mehr. Klar ist nur: Was im Irak passiert, ist eine Tragödie für die Menschen dort. Wenn die Amerikaner den Sieg über einen Terroristen verkünden, dann besagt das gar nichts, der wird sofort ersetzt. al-Qaida kann im Irak tun, was es will, und die Iraker sind die, die darunter leiden. Das war in Vietnam schon so, ein Stellvertreterkrieg.
ZEIT: Auch im Sudan, wo Sie herkommen, ist Krieg. Berührt Sie das noch?
Siddig: Ich habe Familie dort, aber ich fahre nie dahin. Ich habe eine sehr komplizierte Beziehung zum Sudan. Der Sudan ist zu einem schrecklichen Ort geworden, dort herrscht ein Krieg, der von außen finanziert wird, es geht um China gegen Amerika und um Ressourcen. In Darfur gibt es Uran. Es geht nicht um arabische Muslime versus schwarze Christen, da kämpfen von Ausländern bezahlte Warlords gegeneinander. Die Menschen, die dort leben, werden herumgestoßen, wie die Iraker. Aber nicht mal George Clooney, der Syriana gedreht hat, könnte einen Film machen, der Darfur erklärt.
ZEIT: Ihr Onkel Sadiq al-Mahdi war Premierminister des Sudans, bis er in einem Putsch aus dem Amt gejagt wurde. Sie leisten heute humanitäre Hilfe im Sudan.
Siddig: Ich sponsere Helfer, die in Flüchtlingscamps arbeiten. Was ich selber tun könnte, wüsste ich gar nicht. Aber ich habe einen Fanclub, junge engagierte Leute, die unterstütze ich, auch finanziell. Sie helfen beispielsweise sudanesischen Flüchtlingen in Arizona, besorgen ihnen Visa und Wohnungen, bringen sie in Colleges unter. Sie arbeiten auch mit den Ärzten ohne Grenzen zusammen.
ZEIT: Die Rolle, mit der Sie bekannt wurden, war die des Arztes Julian Bashir in dem Star Trek-Ableger Deep Space Nine: Er wird von einem Geheimdienst rekrutiert, der jenen schmutzigen Krieg im All führt, den die ehrenwerte Sternenflotte nicht führen darf. Erinnert Sie diese Konstellation an etwas?
Siddig: Ja, Amerika agiert anders als die UN nach dem Motto: »Der Zweck heiligt die Mittel«. Aber das ist falsch. Deep Space Nine war eine sehr prophetische Serie, die nicht nur schwarz-weiß zeichnete. Da gab es die Sternenkrieger, die Freiheitskämpfer und gleichzeitig Terroristen waren.
ZEIT: Deep Space Nine behandelte politische Themen wie Krieg, Besatzung, Fundamentalismus. Brauchen wir eine neue Deep Space Nine-Folge?
Siddig: Nein, dazu war die Serie viel zu düster. Momentan wollen Amerikaner so etwas nicht sehen, schon die Filme über den Irakkrieg liefen schlecht an der Kasse, ob das nun Rendition war oder In the Valley of Elah. Keiner hat die Kosten wieder eingespielt. Nur mit Filmen wie Spiderman, wo die Guten mit viel Special Effects die Bösen besiegen, wird noch richtig Geld verdient. Es gibt zwar eine Nische für unabhängige Filme, deshalb hat sich Syriana gut geschlagen, aber ein Blockbuster war das auch nicht.
ZEIT: Wird sich das ändern, falls die Demokraten im Weißen Haus ans Ruder kommen?
Siddig: Ich glaube nicht, dass Obama Präsident wird. Die Amerikaner werden nicht für einen schwarzen Mann stimmen. Aber Hollywood hat ohnehin schon mehr für die Verständigung mit der arabischen Welt getan als Washington. So hat Kingdom of Heaven die Kreuzzüge recht real dargestellt, da waren die Christen die Bösen, die aus Gier den Mittleren Osten zerstörten und ausraubten.
ZEIT: Sie selber leben nicht mehr in Hollywood, sondern in England.
Siddig: Ich bin dort weggezogen aus persönlichen Gründen. Deep Space Nine war abgedreht, Bush kam an die Regierung, und ich wurde von meiner Frau, Nana Visitor, geschieden. Aber vor allem hatte ich es satt, zu leben, nur um Geld zu verdienen, und mehr passiert in Hollywood nicht. Ganz generell hat die amerikanische Gesellschaft ein sehr idealisierendes Verhältnis zu Geld, sie verehrt es. Aber es ist schmerzhaft, so zu leben. Ich erlebte in Hollywood Respekt, weil ich viele Dollar verdient habe, und ich wusste, ich verliere Respekt, wenn ich weniger Dollar verdiene. In England genießt ein Dichter oder ein Maler Respekt, auch wenn er arm ist. In England ist meine Seele zu Hause, denn dort bin ich aufgewachsen.
ZEIT: Wie lange wird Hollywood noch der Geschichtenerzähler der Welt sein?
Siddig: Hollywood hat sich bereits verändert. Die großen Studios lösen sich auf, es bilden sich kleinere Labels, weil es so viel verschiedene Zielgruppen und Geschmäcker gibt. Heute werden auch viele Filme gleich für den DVD-Markt gemacht. Die ganz großen Blockbuster sind seltener geworden. Hollywood merkt, dass die USA nicht mehr das wichtigste Land der Welt sind.
Das Gespräch führte Eva Schweitzer
Das sagt der neue Antiheld der TV-Serie »24«, Alexander Siddig
ZEIT ONLINE 26/2008 S. 46 [http://www.zeit.de/2008/26/Interview-Siddig]
Die amerikanische Fernsehserie 24 beschreibt wie keine andere das ambivalente, aus Angst und Aggression gemischte Lebensgefühl der Amerikaner nach dem 11. September: Der Agent Jack Bauer (Kiefer Sutherland), angestellt bei einer fiktiven »Counter Terrorist Unit«, jagt Verschwörer, Terroristen und alle Feinde der Vereinigten Staaten – am liebsten Araber. Hat er die gefasst, foltert er sie, bis sie die Wahrheit preisgeben über eine tickende Bombe oder einen geplanten Atomschlag. Notfalls droht er, ihre Kinder zu ermorden, und rettet so sein Land. Mit dieser Entschlossenheit wurde Jack Bauer in den USA populär, sodass sich bereits republikanische Präsidentschaftskandidaten mit ihm verglichen. Auch bei den US-Soldaten im Irak und in Afghanistan ist die Serie beliebt, und der Chef des Office of Homeland Security ist natürlich Fan. In den USA läuft 24 auf Fox; jede Staffel entspricht einem Tag, jede Folge einer Stunde. In Deutschland lief die Serie bisher auf RTL2, die sechste Staffel beginnt am 23. Juni nun auf ProSieben – mit dem sudanesisch-britischen Schauspieler Alexander Siddig als arabischem Bösewicht.
DIE ZEIT: Herr Siddig, was hat Sie an der Rolle des Hamri Al-Assad interessiert, eines islamischen Terroristen, der im ersten Golfkrieg gegen die USA kämpfte?
Alexander Siddig: Die Figur wirkt zunächst böse, könnte aber auch gut sein. Erst will Hamri Al-Assad bloß Rache, dann paktiert er mit dem amerikanischen Präsidenten, um Frieden zu bewirken. Im Grunde ist er ein Idealist, der Mörder war.
ZEIT: Sein Gegenspieler Jack Bauer foltert gern. Mit diesem reißerischen Konzept haben die Produzenten von 24 gigantische Gewinne gemacht. In den USA wird gerade die siebte Staffel gedreht.
Siddig: Der Grund für den Erfolg ist aber Kiefer Sutherland, der die Hauptrolle spielt, ein großartiger Kollege. Wenn dem der Dialog nicht passt, dann ändert er einfach das Drehbuch. Ich habe das auch versucht, leider nicht so erfolgreich.
ZEIT:24 stilisiert Araber zu Buhmännern. Kennen Sie Jack Shaheens Buch Real Bad Arabs? Darin heißt es, Hollywood stelle Araber seit dem Zweiten Weltkrieg nur noch als böse dar – genau wie Indianer, Schwarze und Japaner.
Siddig: Na ja, vor einer Weile galten Araber als romantisch, denken Sie an Omar Sharif. Mit 9/11gab es eine dramatische Wende, als wir plötzlich zu ganz gefährlichen Leuten wurden. Aber mir persönlich hat das nie viel Ärger bereitet. Wer wird denn von Hollywood nicht negativ stereotypisiert? Auch die Briten und die Deutschen sind immer die Bösen.
ZEIT: Immerhin haben Sie mal beklagt, dass Sie nur noch Rollen als Araber bekämen.
Siddig: Ich habe in The Hamburg Cell Chalid Scheich Mohammed gespielt, den Chefplaner von 9/11. Das hat meine Karriere in Wahrheit befördert. Ich bekam Charakterrollen in Ridley Scotts Kingdom of Heaven, wo es um die Kreuzzüge geht, und in Syriana, wo ich den Prinzen eines arabischen Emirats spielte. Diese Filme wären ohne 9/11 gar nicht geschrieben worden.
ZEIT: Der Prinz endet allerdings tragisch: Er und seine Familie werden von der CIA umgebracht.
Siddig: Ja, aber es war immerhin ein muslimischer Charakter, der ein Herz hatte und der die arabische Welt verbessern wollte. Das sehen wir selten. Und das Timing für den Film war perfekt. Als der auf die Leinwand kam, hatten viele Amerikaner fast vergessen, dass es solche Menschen überhaupt gibt. Stattdessen hatten sie nur wütende Mobs vor den Augen, die vor den TV-Kameras Selbstmordattentate ankündigten. Unser Film hat gezeigt, dass Araber auch Menschen sind.
ZEIT: Das Interessanteste an Syriana waren allerdings amerikanische Secret-Service-Agenten, die insgeheim alles per Fernsteuerung kontrollieren.
Siddig: Ja, und ich habe das Gefühl, so ähnlich ist es auch im Irak. Dabei bin ich mir immer noch nicht sicher, was das Motiv für den Krieg war. Öl, natürlich, aber vielleicht geht es noch um mehr. Klar ist nur: Was im Irak passiert, ist eine Tragödie für die Menschen dort. Wenn die Amerikaner den Sieg über einen Terroristen verkünden, dann besagt das gar nichts, der wird sofort ersetzt. al-Qaida kann im Irak tun, was es will, und die Iraker sind die, die darunter leiden. Das war in Vietnam schon so, ein Stellvertreterkrieg.
ZEIT: Auch im Sudan, wo Sie herkommen, ist Krieg. Berührt Sie das noch?
Siddig: Ich habe Familie dort, aber ich fahre nie dahin. Ich habe eine sehr komplizierte Beziehung zum Sudan. Der Sudan ist zu einem schrecklichen Ort geworden, dort herrscht ein Krieg, der von außen finanziert wird, es geht um China gegen Amerika und um Ressourcen. In Darfur gibt es Uran. Es geht nicht um arabische Muslime versus schwarze Christen, da kämpfen von Ausländern bezahlte Warlords gegeneinander. Die Menschen, die dort leben, werden herumgestoßen, wie die Iraker. Aber nicht mal George Clooney, der Syriana gedreht hat, könnte einen Film machen, der Darfur erklärt.
ZEIT: Ihr Onkel Sadiq al-Mahdi war Premierminister des Sudans, bis er in einem Putsch aus dem Amt gejagt wurde. Sie leisten heute humanitäre Hilfe im Sudan.
Siddig: Ich sponsere Helfer, die in Flüchtlingscamps arbeiten. Was ich selber tun könnte, wüsste ich gar nicht. Aber ich habe einen Fanclub, junge engagierte Leute, die unterstütze ich, auch finanziell. Sie helfen beispielsweise sudanesischen Flüchtlingen in Arizona, besorgen ihnen Visa und Wohnungen, bringen sie in Colleges unter. Sie arbeiten auch mit den Ärzten ohne Grenzen zusammen.
ZEIT: Die Rolle, mit der Sie bekannt wurden, war die des Arztes Julian Bashir in dem Star Trek-Ableger Deep Space Nine: Er wird von einem Geheimdienst rekrutiert, der jenen schmutzigen Krieg im All führt, den die ehrenwerte Sternenflotte nicht führen darf. Erinnert Sie diese Konstellation an etwas?
Siddig: Ja, Amerika agiert anders als die UN nach dem Motto: »Der Zweck heiligt die Mittel«. Aber das ist falsch. Deep Space Nine war eine sehr prophetische Serie, die nicht nur schwarz-weiß zeichnete. Da gab es die Sternenkrieger, die Freiheitskämpfer und gleichzeitig Terroristen waren.
ZEIT: Deep Space Nine behandelte politische Themen wie Krieg, Besatzung, Fundamentalismus. Brauchen wir eine neue Deep Space Nine-Folge?
Siddig: Nein, dazu war die Serie viel zu düster. Momentan wollen Amerikaner so etwas nicht sehen, schon die Filme über den Irakkrieg liefen schlecht an der Kasse, ob das nun Rendition war oder In the Valley of Elah. Keiner hat die Kosten wieder eingespielt. Nur mit Filmen wie Spiderman, wo die Guten mit viel Special Effects die Bösen besiegen, wird noch richtig Geld verdient. Es gibt zwar eine Nische für unabhängige Filme, deshalb hat sich Syriana gut geschlagen, aber ein Blockbuster war das auch nicht.
ZEIT: Wird sich das ändern, falls die Demokraten im Weißen Haus ans Ruder kommen?
Siddig: Ich glaube nicht, dass Obama Präsident wird. Die Amerikaner werden nicht für einen schwarzen Mann stimmen. Aber Hollywood hat ohnehin schon mehr für die Verständigung mit der arabischen Welt getan als Washington. So hat Kingdom of Heaven die Kreuzzüge recht real dargestellt, da waren die Christen die Bösen, die aus Gier den Mittleren Osten zerstörten und ausraubten.
ZEIT: Sie selber leben nicht mehr in Hollywood, sondern in England.
Siddig: Ich bin dort weggezogen aus persönlichen Gründen. Deep Space Nine war abgedreht, Bush kam an die Regierung, und ich wurde von meiner Frau, Nana Visitor, geschieden. Aber vor allem hatte ich es satt, zu leben, nur um Geld zu verdienen, und mehr passiert in Hollywood nicht. Ganz generell hat die amerikanische Gesellschaft ein sehr idealisierendes Verhältnis zu Geld, sie verehrt es. Aber es ist schmerzhaft, so zu leben. Ich erlebte in Hollywood Respekt, weil ich viele Dollar verdient habe, und ich wusste, ich verliere Respekt, wenn ich weniger Dollar verdiene. In England genießt ein Dichter oder ein Maler Respekt, auch wenn er arm ist. In England ist meine Seele zu Hause, denn dort bin ich aufgewachsen.
ZEIT: Wie lange wird Hollywood noch der Geschichtenerzähler der Welt sein?
Siddig: Hollywood hat sich bereits verändert. Die großen Studios lösen sich auf, es bilden sich kleinere Labels, weil es so viel verschiedene Zielgruppen und Geschmäcker gibt. Heute werden auch viele Filme gleich für den DVD-Markt gemacht. Die ganz großen Blockbuster sind seltener geworden. Hollywood merkt, dass die USA nicht mehr das wichtigste Land der Welt sind.
Das Gespräch führte Eva Schweitzer
vendredi 20 juin 2008
The Lethal Phenotype of Cancer
The last decade has seen an explosion in knowledge of the molecular basis and treatment of cancer.
The molecular events that define the lethal phenotype of various cancers—the genetic and cellular alterations that lead to a cancer with a poor or incurable prognosis—are being defined. While these studies describe the cellular events of the lethal phenotype of cancer in detail, how these events result in the common clinical syndromes that kill the majority of cancer patients is not well understood.
It is clear that the central step that makes most cancers incurable is metastasis. Understanding the traits that a cancer acquires to successfully grow and metastasize to distant sites gives insight into how tumors produce multiple factors that result in multiple different clinical syndromes that are lethal for the patient.
CA Cancer J Clin 2007; 57:225-241
The molecular events that define the lethal phenotype of various cancers—the genetic and cellular alterations that lead to a cancer with a poor or incurable prognosis—are being defined. While these studies describe the cellular events of the lethal phenotype of cancer in detail, how these events result in the common clinical syndromes that kill the majority of cancer patients is not well understood.
It is clear that the central step that makes most cancers incurable is metastasis. Understanding the traits that a cancer acquires to successfully grow and metastasize to distant sites gives insight into how tumors produce multiple factors that result in multiple different clinical syndromes that are lethal for the patient.
CA Cancer J Clin 2007; 57:225-241
Ordres de grandeur
Ordres de grandeur
Millions, milliards, billions d'euro... On a l'habitude de jongler avec de tels montants dans les secteurs capitalistiques comme l'aéronautique ou l'énergie.
Voici enfin les valeurs typiques classés par ordre croissant, histoire de mieux distinguer les dépenses quasi-banales et les projets pharaoniques.
100 millions d'euro
* Fusée Ariane 5 (sans satellite) prête à lancer : 100 millions d'euro
* Super-méthanier : 200 millions d'euro
* Airbus A380 : 300 millions de dollars prix catalogue (pour mémoire)
* Ferme éolienne offshore (150 MW installés) : 200-800 millions de dollars
* Terminal méthanier : 500 millions d'euro
* Plateforme pétrolière off-shore (production de 50 Mbbl/an) : 500 millions de dollars
1 milliard d'euro
* Centrale au charbon moderne (850 MW) : 1 milliard d'euro
* Russia Tower (gratte-ciel de 600 mètres de haut) : 1,5 milliard d'euro
* Rémunération individuelle 2007 de grands gérants de hedge funds : 2 milliards d'euro (3 à 4 milliards de dollars pour des stars de Wall Street comme Paulson, Soros ou Simons, selon Les Echos)
* Réacteur nucléaire EPR "tête de série" : 3 milliards d'euro (montant officiel du projet OL3, réacteur EPR clé-en-main construit par Areva en Finlande)
* Revenus journaliers consolidés des pays producteurs de pétrole (2007) : 5 milliards d'euro (estimation)
10 milliards d'euro
* Budget total du projet ITER : 10 milliards d'euro
* Développement de l'Airbus A380 : 11 milliards d'euro (pour mémoire)
* Tunnel sous la Manche : 16 milliards d'euro (pour mémoire)
* Barrage des Trois-Gorges : 25 milliards d'euro (montant prévu - et sans doute largement dépassé - des dépenses au démarrage du projet)
* Investissements mondiaux 2006 dans les énergies renouvelables : 56 milliards d'euro. Source : PNUE. On parle souvent de 100 milliards de dollars, mais 30% correspondent à des opérations financières (fusions/acquisitions)
* Réseau HVDC Afrique-Europe (Réseau hypothétique permettant le transport massif d'électricité produite en Afrique (solaire concentré) vers les centres de consommation européens.) : 60 milliards d'euro
100 milliards d'euro
* Programme Apollo : 100 milliards d'euro 2006. Selon wikipedia, 25 milliards de dollars 1969
* Investissements en exploration-production pétrolière (2006) : 275 milliards de dollars
* Capitalisation boursière d'ExxonMobil : environ 500 milliards de dollars. ExxonMobil est la plus importante capitalisation boursière mondiale... après PetroChina.
* Investissements annuels à engager pour atténuer les effets du changement climatique : 500 milliards d'euro (1% du PIB mondial selon le rapport Stern)
* Pertes dûes à la crise financière de 2007-2008 : 600 milliards d'euro (945 milliards de dollars, estimation du FMI au 8 avril 2008)
* Dépenses militaires mondiales (2005) : 900 milliards d'euro
1000 milliards d'euro (ou un billion d'euro, en bon français)
* Montant total moyen des investissements annuels nécessaires en infrastructures pour répondre à la demande en énergie sur la période 2005-2030 : 1 000 milliards d'euro 2005 - Source : ''World Energy Outlook'', AIE
* Capitaux gérés par les fonds d'arbitrage (hedge funds) en 2007 : 1 250 milliards d'euro (selon le Monde)
* Revenus annuels consolidés des pays producteurs de pétrole : 2 000 milliards d'euro
* PIB France : 2 000 milliards d'euro
* création monétaire mondiale annuelle : 5 000 milliards d'euro
10 000 milliards d'euro
* Capitalisation boursière consolidée du New York Stock Exchange : environ 15 000 milliards d'euro
* Dette privée mondiale : 20 000 milliards d'euro
* PIB Monde : 45 000 milliards d'euro
jeudi 19 juin 2008
DERNIERES CARTOUCHES ET FONDS DE TIROIR .....
Les réserves des USA étaient jusque là considérées comme stratégiques et à utiliser en dernier ressort.
Les USA seraient donc prêts à commencer à brûler leurs dernières cartouches.
George Bush demande la levée de l'interdiction du forage pétrolier en mer
LEMONDE.FR avec AP et AFP | 18.06.08 | 19h33 • Mis à jour le 18.06.08 | 19h43
Estimant que les Etats-Unis doivent "produire davantage de pétrole dès à présent" pour faire face à la flambée du prix du pétrole, le président américain, George W. Bush, a demandé au Congrès de lever l'interdiction du forage en mer, une mesure à laquelle il a pourtant été longtemps lui-même opposé. "Tout délai serait inexcusable", a ajouté M. Bush à l'adresse des parlementaires, dans un communiqué diffusé mercredi 18 juin. Il leur demande dans un premier temps de légiférer sur le sujet, promettant de lever l'interdiction qu'il avait prononcé contre tout forage en mer.
Un moratoire interdisant le forage en mer à la recherche de pétrole et de gaz naturel existe aux Etats-Unis depuis 1981, afin de protéger le tourisme et minimiser la possibilité d'une marée noire sur les côtes américaines. Le président américain a également demandé au Congrès d'autoriser le forage dans l'Arctic National Wildlife, une réserve naturelle en Alaska jusque-là interdite à l'exploitation pétrolière, ainsi que dans les zones autour du Green River Basin dans les Etats du Colorado, de l'Utah et du Wyoming.
Selon M. Bush, la levée de ce moratoire pourrait augmenter la production de pétrole de près de 18 milliards de barils, tout en admettant qu'il faudrait plusieurs années pour atteindre ce niveau. Le département de l'énergie américain estime, pour sa part, que les zones couvertes par le moratoire contiennent 16 milliards de barils.
UN SUJET BRÛLANT DE LA CAMPAGNE AMÉRICAINE
L'initiative émanant de la Maison Blanche intervient alors que le prix du baril a atteint 130 dollars et que la question s'est imposée comme un des principaux thèmes de la campagne présidentielle. Le candidat républicain, John McCain, a publiquement pris position pour l'ouverture du forage en mer, mardi à Houston, fief historique de l'industrie pétrolière, et plusieurs républicains de haut rang ont appelé à la fin du moratoire.
L'administration Bush s'en est prise aux législateurs démocrates, majoritaires à l'Assemblée et au Sénat, accusés de ralentir sciemment le processus et de pénaliser le peuple américain. Et si aucune mesure n'est prise d'ici au 4 juillet, "les Américains pourront se demander à juste titre jusqu'où les prix devront augmenter pour que le Congrès démocrate agisse enfin", a ajouté le président américain.
Le candidat démocrate Barack Obama s'est montré jusqu'ici opposé à la levée du moratoire, prônant la conservation des milieux naturels et le développement des énergies alternatives pour faire face à la crise du pétrole.
Bush Calls for End to Ban on Offshore Oil Drilling
By SHERYL GAY STOLBERG
WASHINGTON — President Bush urged Congress on Wednesday to end a federal ban on offshore oil drilling and open a portion of the Arctic National Wildlife Refuge for oil exploration, asserting that those steps and others would lower gasoline prices and “strengthen our national security.”
In recent years, the president said, “scientists have developed innovative techniques to reach Anwar’s oil with virtually no impact on the land or local wildlife,” referring to the wildlife refuge by its acronym. He continued, “I urge members of Congress to allow this remote region to bring enormous benefits to the American people.”
President Bush also urged Congress to approve the extraction of oil from shale on federal lands, something he said can be done far more economically now than a few years ago, and to speed the approval process for building new refineries.
Mr. Bush sought to take full political advantage of soaring fuel prices by portraying Republican lawmakers as imaginative and forward-looking and the Democratic majority in Congress as obstructionists on energy policy.
“I know the Democratic leaders have opposed some of these policies in the past,” Mr. Bush said. “Now that their opposition has helped drive gas prices to record levels, I ask them to reconsider their positions. If Congressional leaders leave for the Fourth of July recess without taking action, they will need to explain why $4-a-gallon gasoline is not enough incentive for them to act.”
The president’s move to end the ban on offshore drilling reverses his longstanding position on the issue. Together with the other proposals he laid out on Wednesday, it underscores how $4-a-gallon gas has become a major issue in the 2008 presidential campaign. A growing number of Republicans are lining up in opposition to the federal ban.
The party’s presumptive presidential nominee, Senator John McCain of Arizona, used a speech in Houston on Tuesday to say he now favors offshore drilling, an announcement that infuriated environmentalists who had long viewed him as an ally. Florida’s Republican governor, Charlie Crist, immediately joined Mr. McCain, saying that he, too, now wants an end to the ban.
Senator Harry Reid of Nevada, the Democratic majority leader, reacted quickly to the president’s remarks on Wednesday. “This week’s flip-flop on offshore oil drilling by President Bush and Senator John McCain is nothing more than a cynical campaign ploy that will do nothing to lower energy prices, and represents another big giveaway to oil companies already making billions in profits,” Mr. Reid said in a statement.
On Tuesday, before Mr. Bush’s decision became known, the drilling issue was already causing a heated back-and-forth on the campaign trail. Mr. McCain sought to straddle the divide between environmentalists and the energy industry, while facing accusations from his Democratic opponent, Senator Barack Obama, that he had capitulated to the oil industry.
Mr. Bush has said for years that he favors opening up the Arctic National Wildlife Refuge to drilling, and in 2006 he signed into law a bill that expanded exploration in the Gulf of Mexico. But the topic of coastal drilling elsewhere has been an extremely sensitive one in the Bush family; Mr. Bush’s father signed a presidential executive order in 1990 banning coastal oil exploration, and Mr. Bush’s brother Jeb was an outspoken opponent of offshore drilling when he was governor of Florida.
Now, though, President Bush is considering retracting his father’s order. Although the chief White House spokeswoman, Dana Perino, said Mr. Bush “is not taking any executive action” on Wednesday, two people outside the White House said such a move was under serious consideration, and a senior White House official did not dispute their account.
“This is a strong point of discussion inside the White House,” said Representative John E. Peterson, a Pennsylvania Republican who has been asking Mr. Bush for years to rescind his father’s action. Mr. Peterson is also leading an effort in Congress to repeal its ban.
Offshore drilling is blocked by two bans, one imposed by Congress and the other by the first President Bush’s executive order. Asked why the current President Bush did not act at once to lift the order imposed by his father, Keith Hennessey, the director of the president’s economic council, told White House reporters, “He thinks that probably the most productive way to work with this Congress is to try to do it in tandem.”
But the Institute for Energy Research, a nonprofit research organization that promotes “free-market energy and environmental policy,” has called for Mr. Bush to rescind the executive order and chided him on Wednesday for not doing so. “The president has chosen to speak softly when American consumers need him to wield a big stick,” the group’s president, Thomas J. Pyle, said in a statement on Wednesday. “This was a missed opportunity.”
Later, a White House spokesman, Tony Fratto, defended Mr. Bush’s refusal so far to lift the executive order. “The President turning his key alone isn’t going to do it,” Mr. Fratto said. “But he made perfectly clear that he will turn that key, that he will lift, or that he will announce the withdrawal if Congress can take action.”
With oil selling for more than $130 a barrel in the commodity markets and no end in sight to high gasoline prices, Mr. Bush, a former oilman from Texas who came into office vowing to address an impending energy shortage, does not want to end his presidency in the midst of an energy crisis.
No one knows for certain how much oil is in the moratorium area. The federal Energy Information Administration estimates that roughly 75 billion barrels of oil in the United States may be found in all areas of the country that are now off limits for development, and that 21 percent of this oil — or about 16 billion barrels — is covered by the offshore moratorium.
Mr. Bush’s new stance on offshore drilling will inject him squarely into the presidential campaign, by putting the full weight of the White House behind Mr. McCain at a time when the candidate is trying to demonstrate presidential stature. But it will also expose Mr. McCain to accusations from Democrats that a McCain presidency would be akin to a Bush third term.
At the same time, the move will put the onus on Democrats, many of whom have long been staunchly opposed to offshore drilling. And it is likely to exacerbate the 30-year-old standoff in Washington over whether domestic drilling or conservation is the way to end American dependence on foreign oil.
That debate has grown especially acute in recent weeks, with the White House in “I told you so” mode. In a speech to the United States Chamber of Commerce last week, Vice President Dick Cheney said, “We should hear no more complaining” from opponents of domestic drilling, whom he called “part of the problem.”
Senator Reid responded by calling the vice president “Oil Man Cheney,” saying: “So all that Cheney can talk about, the Oil Man Cheney can talk about, is drilling, drilling, drilling. But there is not enough oil in America to make that the salvation to our problems.”
After hearing of Mr. Bush’s proposal on Tuesday night, Mr. Reid affirmed his opposition, saying, “The Energy Information Administration says that even if we open the coasts to oil drilling that won’t have a significant impact on prices.”
After President Bush’s remarks on Wednesday, Mr. Reid said: “The facts are clear. Oil companies have already had ample opportunity to increase supply, but they have sat on their hands. They aren’t even using more than half of the public lands they already have leased for drilling. And despite the huge tax breaks President Bush and Republican Congresses have given oil and gas companies to invest in refineries, domestic production has actually dropped.” And the House speaker, Nancy Pelosi, said, “The president’s proposal sounds like another page from the administration’s energy policy that was literally written by the oil industry: give away more public resources to the very same oil companies that are sitting on 68 million acres of federal lands they’ve already leased.”
The Congressional moratorium was first enacted in 1982, and has been renewed every year since. It prohibits oil and gas leasing on most of the outer continental shelf, 3 miles to 200 miles offshore. Since 1990, it has been supplemented by the first President Bush’s executive order, which directed the Interior Department until 2000 not to conduct offshore leasing or pre-leasing activity in areas covered by the legislative ban. In 1998, President Bill Clinton extended the offshore leasing prohibition until 2012. One person familiar with the deliberations inside the White House said that Mr. Bush was briefed on Tuesday by his top aides, including Joshua B. Bolten, the chief of staff, and that the aides recommended lifting the executive order.
On Capitol Hill, Republicans are proposing several bills to undo the ban. They differ on how close to shore drilling could begin, but all would give states a veto on oil exploration within 100 miles of their coastlines. Ms. Perino said Mr. Bush believed Congress should pass one of the bills, so the federal government and the states could work together to share revenues from exploration.
The issue does not fall entirely along party lines. One prominent Republican opponent of drilling, Gov. Arnold Schwarzenegger of California, does not intend to change his stance, a spokesman said Tuesday. In Houston, meanwhile, Mr. McCain, who has long been at odds with Mr. Bush on another environmental issue, climate change, tried to distance himself from the White House.
In a speech to oil industry executives and business and community leaders, the senator implicitly criticized Mr. Cheney, who in 2001 dismissed conservation as a “personal virtue.” Mr. McCain said the next president would have to break with the policies of the past, adding, “In the face of climate change and other serious challenges, energy conservation is no longer just a moral luxury or a personal virtue.”
On the issue of offshore drilling, Douglas Holtz-Eakin, Mr. McCain’s domestic policy adviser, said the senator had supported the moratorium until a compromise was reached in late 2006 between the federal government and Gulf Coast states that permitted oil and gas exploration in a vast area mostly 100 miles from shore.
“Prior to that, he favored the moratorium as a way to support states’ opposition to exploration,” Mr. Holtz-Eakin said.
But Mr. Obama, campaigning in Michigan, swiftly pointed out that Mr. McCain had supported the moratorium during his 2000 presidential run. “His decision to completely change his position and tell a group of Houston oil executives exactly what they wanted to hear today was the same Washington politics that has prevented us from achieving energy independence for decades,” Mr. Obama said in a statement.
Reporting was contributed by Carl Hulse from Washington; Elisabeth Bumiller from Houston; Jeff Zeleny from Taylor, Mich.; Jad Mouawad from New York; and David M. Herszenhorn and David Stout from Washington
Les USA seraient donc prêts à commencer à brûler leurs dernières cartouches.
George Bush demande la levée de l'interdiction du forage pétrolier en mer
LEMONDE.FR avec AP et AFP | 18.06.08 | 19h33 • Mis à jour le 18.06.08 | 19h43
Estimant que les Etats-Unis doivent "produire davantage de pétrole dès à présent" pour faire face à la flambée du prix du pétrole, le président américain, George W. Bush, a demandé au Congrès de lever l'interdiction du forage en mer, une mesure à laquelle il a pourtant été longtemps lui-même opposé. "Tout délai serait inexcusable", a ajouté M. Bush à l'adresse des parlementaires, dans un communiqué diffusé mercredi 18 juin. Il leur demande dans un premier temps de légiférer sur le sujet, promettant de lever l'interdiction qu'il avait prononcé contre tout forage en mer.
Un moratoire interdisant le forage en mer à la recherche de pétrole et de gaz naturel existe aux Etats-Unis depuis 1981, afin de protéger le tourisme et minimiser la possibilité d'une marée noire sur les côtes américaines. Le président américain a également demandé au Congrès d'autoriser le forage dans l'Arctic National Wildlife, une réserve naturelle en Alaska jusque-là interdite à l'exploitation pétrolière, ainsi que dans les zones autour du Green River Basin dans les Etats du Colorado, de l'Utah et du Wyoming.
Selon M. Bush, la levée de ce moratoire pourrait augmenter la production de pétrole de près de 18 milliards de barils, tout en admettant qu'il faudrait plusieurs années pour atteindre ce niveau. Le département de l'énergie américain estime, pour sa part, que les zones couvertes par le moratoire contiennent 16 milliards de barils.
UN SUJET BRÛLANT DE LA CAMPAGNE AMÉRICAINE
L'initiative émanant de la Maison Blanche intervient alors que le prix du baril a atteint 130 dollars et que la question s'est imposée comme un des principaux thèmes de la campagne présidentielle. Le candidat républicain, John McCain, a publiquement pris position pour l'ouverture du forage en mer, mardi à Houston, fief historique de l'industrie pétrolière, et plusieurs républicains de haut rang ont appelé à la fin du moratoire.
L'administration Bush s'en est prise aux législateurs démocrates, majoritaires à l'Assemblée et au Sénat, accusés de ralentir sciemment le processus et de pénaliser le peuple américain. Et si aucune mesure n'est prise d'ici au 4 juillet, "les Américains pourront se demander à juste titre jusqu'où les prix devront augmenter pour que le Congrès démocrate agisse enfin", a ajouté le président américain.
Le candidat démocrate Barack Obama s'est montré jusqu'ici opposé à la levée du moratoire, prônant la conservation des milieux naturels et le développement des énergies alternatives pour faire face à la crise du pétrole.
Bush Calls for End to Ban on Offshore Oil Drilling
By SHERYL GAY STOLBERG
WASHINGTON — President Bush urged Congress on Wednesday to end a federal ban on offshore oil drilling and open a portion of the Arctic National Wildlife Refuge for oil exploration, asserting that those steps and others would lower gasoline prices and “strengthen our national security.”
In recent years, the president said, “scientists have developed innovative techniques to reach Anwar’s oil with virtually no impact on the land or local wildlife,” referring to the wildlife refuge by its acronym. He continued, “I urge members of Congress to allow this remote region to bring enormous benefits to the American people.”
President Bush also urged Congress to approve the extraction of oil from shale on federal lands, something he said can be done far more economically now than a few years ago, and to speed the approval process for building new refineries.
Mr. Bush sought to take full political advantage of soaring fuel prices by portraying Republican lawmakers as imaginative and forward-looking and the Democratic majority in Congress as obstructionists on energy policy.
“I know the Democratic leaders have opposed some of these policies in the past,” Mr. Bush said. “Now that their opposition has helped drive gas prices to record levels, I ask them to reconsider their positions. If Congressional leaders leave for the Fourth of July recess without taking action, they will need to explain why $4-a-gallon gasoline is not enough incentive for them to act.”
The president’s move to end the ban on offshore drilling reverses his longstanding position on the issue. Together with the other proposals he laid out on Wednesday, it underscores how $4-a-gallon gas has become a major issue in the 2008 presidential campaign. A growing number of Republicans are lining up in opposition to the federal ban.
The party’s presumptive presidential nominee, Senator John McCain of Arizona, used a speech in Houston on Tuesday to say he now favors offshore drilling, an announcement that infuriated environmentalists who had long viewed him as an ally. Florida’s Republican governor, Charlie Crist, immediately joined Mr. McCain, saying that he, too, now wants an end to the ban.
Senator Harry Reid of Nevada, the Democratic majority leader, reacted quickly to the president’s remarks on Wednesday. “This week’s flip-flop on offshore oil drilling by President Bush and Senator John McCain is nothing more than a cynical campaign ploy that will do nothing to lower energy prices, and represents another big giveaway to oil companies already making billions in profits,” Mr. Reid said in a statement.
On Tuesday, before Mr. Bush’s decision became known, the drilling issue was already causing a heated back-and-forth on the campaign trail. Mr. McCain sought to straddle the divide between environmentalists and the energy industry, while facing accusations from his Democratic opponent, Senator Barack Obama, that he had capitulated to the oil industry.
Mr. Bush has said for years that he favors opening up the Arctic National Wildlife Refuge to drilling, and in 2006 he signed into law a bill that expanded exploration in the Gulf of Mexico. But the topic of coastal drilling elsewhere has been an extremely sensitive one in the Bush family; Mr. Bush’s father signed a presidential executive order in 1990 banning coastal oil exploration, and Mr. Bush’s brother Jeb was an outspoken opponent of offshore drilling when he was governor of Florida.
Now, though, President Bush is considering retracting his father’s order. Although the chief White House spokeswoman, Dana Perino, said Mr. Bush “is not taking any executive action” on Wednesday, two people outside the White House said such a move was under serious consideration, and a senior White House official did not dispute their account.
“This is a strong point of discussion inside the White House,” said Representative John E. Peterson, a Pennsylvania Republican who has been asking Mr. Bush for years to rescind his father’s action. Mr. Peterson is also leading an effort in Congress to repeal its ban.
Offshore drilling is blocked by two bans, one imposed by Congress and the other by the first President Bush’s executive order. Asked why the current President Bush did not act at once to lift the order imposed by his father, Keith Hennessey, the director of the president’s economic council, told White House reporters, “He thinks that probably the most productive way to work with this Congress is to try to do it in tandem.”
But the Institute for Energy Research, a nonprofit research organization that promotes “free-market energy and environmental policy,” has called for Mr. Bush to rescind the executive order and chided him on Wednesday for not doing so. “The president has chosen to speak softly when American consumers need him to wield a big stick,” the group’s president, Thomas J. Pyle, said in a statement on Wednesday. “This was a missed opportunity.”
Later, a White House spokesman, Tony Fratto, defended Mr. Bush’s refusal so far to lift the executive order. “The President turning his key alone isn’t going to do it,” Mr. Fratto said. “But he made perfectly clear that he will turn that key, that he will lift, or that he will announce the withdrawal if Congress can take action.”
With oil selling for more than $130 a barrel in the commodity markets and no end in sight to high gasoline prices, Mr. Bush, a former oilman from Texas who came into office vowing to address an impending energy shortage, does not want to end his presidency in the midst of an energy crisis.
No one knows for certain how much oil is in the moratorium area. The federal Energy Information Administration estimates that roughly 75 billion barrels of oil in the United States may be found in all areas of the country that are now off limits for development, and that 21 percent of this oil — or about 16 billion barrels — is covered by the offshore moratorium.
Mr. Bush’s new stance on offshore drilling will inject him squarely into the presidential campaign, by putting the full weight of the White House behind Mr. McCain at a time when the candidate is trying to demonstrate presidential stature. But it will also expose Mr. McCain to accusations from Democrats that a McCain presidency would be akin to a Bush third term.
At the same time, the move will put the onus on Democrats, many of whom have long been staunchly opposed to offshore drilling. And it is likely to exacerbate the 30-year-old standoff in Washington over whether domestic drilling or conservation is the way to end American dependence on foreign oil.
That debate has grown especially acute in recent weeks, with the White House in “I told you so” mode. In a speech to the United States Chamber of Commerce last week, Vice President Dick Cheney said, “We should hear no more complaining” from opponents of domestic drilling, whom he called “part of the problem.”
Senator Reid responded by calling the vice president “Oil Man Cheney,” saying: “So all that Cheney can talk about, the Oil Man Cheney can talk about, is drilling, drilling, drilling. But there is not enough oil in America to make that the salvation to our problems.”
After hearing of Mr. Bush’s proposal on Tuesday night, Mr. Reid affirmed his opposition, saying, “The Energy Information Administration says that even if we open the coasts to oil drilling that won’t have a significant impact on prices.”
After President Bush’s remarks on Wednesday, Mr. Reid said: “The facts are clear. Oil companies have already had ample opportunity to increase supply, but they have sat on their hands. They aren’t even using more than half of the public lands they already have leased for drilling. And despite the huge tax breaks President Bush and Republican Congresses have given oil and gas companies to invest in refineries, domestic production has actually dropped.” And the House speaker, Nancy Pelosi, said, “The president’s proposal sounds like another page from the administration’s energy policy that was literally written by the oil industry: give away more public resources to the very same oil companies that are sitting on 68 million acres of federal lands they’ve already leased.”
The Congressional moratorium was first enacted in 1982, and has been renewed every year since. It prohibits oil and gas leasing on most of the outer continental shelf, 3 miles to 200 miles offshore. Since 1990, it has been supplemented by the first President Bush’s executive order, which directed the Interior Department until 2000 not to conduct offshore leasing or pre-leasing activity in areas covered by the legislative ban. In 1998, President Bill Clinton extended the offshore leasing prohibition until 2012. One person familiar with the deliberations inside the White House said that Mr. Bush was briefed on Tuesday by his top aides, including Joshua B. Bolten, the chief of staff, and that the aides recommended lifting the executive order.
On Capitol Hill, Republicans are proposing several bills to undo the ban. They differ on how close to shore drilling could begin, but all would give states a veto on oil exploration within 100 miles of their coastlines. Ms. Perino said Mr. Bush believed Congress should pass one of the bills, so the federal government and the states could work together to share revenues from exploration.
The issue does not fall entirely along party lines. One prominent Republican opponent of drilling, Gov. Arnold Schwarzenegger of California, does not intend to change his stance, a spokesman said Tuesday. In Houston, meanwhile, Mr. McCain, who has long been at odds with Mr. Bush on another environmental issue, climate change, tried to distance himself from the White House.
In a speech to oil industry executives and business and community leaders, the senator implicitly criticized Mr. Cheney, who in 2001 dismissed conservation as a “personal virtue.” Mr. McCain said the next president would have to break with the policies of the past, adding, “In the face of climate change and other serious challenges, energy conservation is no longer just a moral luxury or a personal virtue.”
On the issue of offshore drilling, Douglas Holtz-Eakin, Mr. McCain’s domestic policy adviser, said the senator had supported the moratorium until a compromise was reached in late 2006 between the federal government and Gulf Coast states that permitted oil and gas exploration in a vast area mostly 100 miles from shore.
“Prior to that, he favored the moratorium as a way to support states’ opposition to exploration,” Mr. Holtz-Eakin said.
But Mr. Obama, campaigning in Michigan, swiftly pointed out that Mr. McCain had supported the moratorium during his 2000 presidential run. “His decision to completely change his position and tell a group of Houston oil executives exactly what they wanted to hear today was the same Washington politics that has prevented us from achieving energy independence for decades,” Mr. Obama said in a statement.
Reporting was contributed by Carl Hulse from Washington; Elisabeth Bumiller from Houston; Jeff Zeleny from Taylor, Mich.; Jad Mouawad from New York; and David M. Herszenhorn and David Stout from Washington
Nanterre, France, Préfecture des Hauts de Seine , arrestations au guichet, en "cabine fermée" .... 1943 ? non, 2008 ! Qu'en pense Jean Sarkozy de Nag
Nanterre, France, Préfecture des Hauts de Seine , arrestations au guichet, en "cabine fermée" .... 1943 ? non, 2008 ! Qu'en pense l'élu de la République Jean Sarkozy de Nagy Bocsa ?
POUR LIRE CE DOCUMENT OFFICIEL (en pdf)
Et vous, qu'en pensez vous ? ..... Prémices d'un "Retour vers le futur" peut-être ?
Adresse internet de ce glorieux établissement de notre fière République : http://www.hauts-de-seine.pref.gouv.fr/newspage.php?id=1&pg=5
mercredi 18 juin 2008
la banane ne dégage pas assez d'ondes pour cuire du pop-corn
COMME LE RECOMMANDE CETTE TRES AMUSANTE PETITE VIDEO, ATTENTION AUX BANANES, ET, SURTOUT, AIGUISONS NOTRE ESPRIT CRITIQUE ....... ------->>>
Preuves scientifiques du danger pour la santé de la téléphonie mobile : le rapport 'Bioinitiative' (2007)
A Rationale for a Biologically-based Public Exposure Standard for Electromagnetic Fields (ELF and RF)
Résumé en Français du contenu de ce rapport :
Comité organisateur
Carl F. BLACKMAN – Martin BLANK – Michael KUNDI – Cindy SAGE
Signataires d'articles
David O. CARPENTER - Zoreh DAVANIPOUR - David GEE - Lennart HARDELL - Olle JOHANSSON - Henry LAI - Kjell Hansson MILD - Amy SAGE - Eugene L. SOBEL - Zhengping XU - Guangdi CHEN
Ont participé
James B. BURCH - Nancy EVANS - Stanton GLANZ - Denis HENSHAW - Samuel MILHAM - Louis SLESIN
Tous ces scientifiques sont des sommités dans l'étude des effets des divers types de champs électromagnétiques sur toutes les formes du vivant.
Les membres du Comité Organisateur et trois des signataires sont membres de la très renommée BIOELECTROMAGNETICS SOCIETY.
Ce rapport récapitulatif passe en revue plus de 1500 travaux publiés. Il constitue une première sur ce sujet, car il est rédigé sous l'égide des mots PREUVES SCIENTIFIQUES
A noter l'absence de lien financier ou public des rédacteurs avec l'industrie ou les autorités politiques et administratives de régulation des télécommunications.
Articulation du rapport :
Note technique sur les émissions dont les effets sont traités par le rapport :
Les émissions de téléphonie mobile ont une structure physique triple :
> Une hyperfréquence dite porteuse
> des modulations en extrêmement basses fréquences pour les signaux portés
> une multipulsation chaotique.
Chaque structure a sa toxicité propre, la pire étant la multipulsation.
Les émissions UMTS – WIFI – WIMAX – BLUETOOTH – DECT - sont de la même famille de structure que la téléphonie mobile. Les toxicités sont de même nature.
Nous appellerons ces émissions TTM – Type Téléphonie Mobile.
Début du rapport - Textes de présentation
- Article 4 : PREUVES DE L'INADAPTATION DES NORMES
C'est-à-dire preuves du fait que les documents et chiffres officiels censés garantir une protection n'en assurent aucune.
Auteur : Cindy SAGE
Membre titulaire de la BS – BIOELECTROMAGNETICS SOCIETY
Travaux publiés cités en référence ……………………………………….4
- Article 5 : PREUVES DES EFFETS GENETIQUES
C'est-à-dire preuves du fait que l'exposition du vivant à des émissions TTM provoque des effets sur les gènes et sur l'expression des protéines.
Auteurs : Zhengping XU et Guangdi CHEN – Membres de la BS
Membres de l'Université de Médecine ZHEJIANG à HANSZOU - CHINE
Travaux publiés cités en référence …………………………………….35
- Article 6 : PREUVES DES EFFETS GENOTOXIQUES ET DES DOMMAGES GENETIQUES
C'est-à-dire preuves du fait que l'exposition du vivant à des émissions TTM provoque des altérations non réparables de l'ADN.
Auteur : Dr Henry LAI
Université de WASHINGTON – USA
Travaux publiés cités en référence ……………………………………220
- Article 7 : PREUVES DES EFFETS SUR LES PROTEINES DE STRESS
C'est-à-dire preuves du fait que l'exposition du vivant à des émissions TTM déclenche des processus de mise en oeuvre des protéines de stress.
Auteur : Dr Martin BLANK – Président de la BS
Université de COLUMBIA – NEW YORK – USA
Travaux publiés cités en référence ……………………………………196
- Article 8 : PREUVES DES EFFETS SUR LA FONCTION IMMUNITAIRE
C'est-à-dire preuves du fait que l'exposition du vivant à des émissions TTM provoque des perturbations de fonctionnement du système immunitaire.
Auteur : Dr Olle JOHANSSON
Institut KAROLINSKA - STOCKHOLM – SUEDE
Travaux publiés cités en référence ………………………………..……70
- Article 9 : PREUVES DES EFFETS SUR LA NEUROLOGIE ET LE COMPORTEMENT
C'est-à-dire preuves du fait que l'exposition du vivant à des émissions TTM provoque des perturbations de fonctionnement du système nerveux qui ont pour conséquences des troubles du comportement.
Cet article traite également du fait que ces émissions provoquent une importante perte d'étanchéité de la barrière sang-cerveau au niveau des vaisseaux irrigant le cerveau.
Auteur : Dr Henry LAI
Université de WASHINGTON – USA
Travaux publiés cités en référence ………………………………..…..375
- Article 10 : PREUVES SUR L'ORIGINE DE TUMEURS DU CERVEAU ET DE NEURINOMES ACOUSTIQUES
C'est-à-dire preuves du fait que l'exposition du vivant à des émissions TTM déclenche des processus de développement de tumeurs du cerveau et de neurinomes acoustiques.
Auteurs : - Dr Lennart HARDELL
Hôpital Universitaire d'OREBRO – SUEDE
- Dr Kjell Hansson MILD – Président de la BS Université d'UMEA – SUEDE
- Dr Michael KUNDI – Membre titulaire de la BS Université Médicale de VIENNE – AUTRICHE
Travaux publiés cités en référence …………………………………148
- Article 11 : PREUVES SUR L'ORIGINE DE CANCERS ENFANTINS – LEUCEMIE
C'est-à-dire preuves du fait que l'exposition du vivant à des émissions TTM déclenche des processus de développement de cancers enfantins du type leucémie.
Auteur : Dr Michael KUNDI – Membre titulaire de la BS Université Médicale de VIENNE – AUTRICHE
Travaux publiés cités en référence …………………………………118
- Article 12 : EFFETS SUR LA PRODUCTION DE MELATONINE, SUR LA MALADIE D'ALZHEIMER ET SUR LES CANCERS DU SEIN
L'article traite des preuves du fait que l'exposition du vivant à des émissions TTM perturbe le taux de production de la mélatonine et déclenche des processus de développement de la maladie d'ALZHEIMER et de cancers du sein.
Auteurs : - Dr Zoreh DAVANIPOUR
Institut FRIENDS RESEARCH – LOS ANGELES – USA
- Dr Eugene L. SOBEL
Institut FRIENDS RESEARCH – LOS ANGELES – USA
Travaux publiés cités en référence …………………………………171
- Article 13 : PREUVES SUR L'ORIGINE DES CANCERS DU SEIN
C'est-à-dire preuves du fait que l'exposition du vivant à des émissions TTM déclenche des processus de développement de cancers du sein.
Auteur : Cindy SAGE – Membre titulaire de la BS
Travaux publiés cités en référence ………………….………………….50
- Article 14 : PREUVES SUR L'ORIGINE DES PERTURBATIONS DES REGULATIONS MEMBRANAIRES
C'est-à-dire preuves du fait que l'exposition du vivant à des émissions TTM provoque des perturbations dans la régulation des échanges cellulaires au niveau des canaux ioniques des membranes. Et donc, une perturbation de l'ensemble des fonctions vitales au niveau physiologique élémentaire, celui de la cellule.
Auteur : Carl F. BLACKMAN – Président de la BS
US Environmental Protection Agency – USA
Travaux publiés cités en référence ………………………………..……74
- Article 15 : PREUVES FONDEES SUR LES THERAPIES MEDICALES
C'est-à-dire preuves de l'existence de divers types d'effets que l'exposition à des émissions TTM a sur le vivant par l'efficacité de thérapies qui mettent en oeuvre les aspects positifs de ces effets.
Auteurs : - Cindy SAGE – Membre titulaire de la BS
- Amy SAGE
Travaux publiés cités en référence ……………………………..……17
- Article 16 : LE PRINCIPE DE PRECAUTION
Auteur : Mr David GEE
Agence Européenne de l'Environnement – COPENHAGUE – DANEMARK
Travaux publiés cités en référence ……………………………...………57
- Article 17 : CLEF DES PREUVES SCIENTIFIQUES
Auteurs : - Dr David O. CARPENTER
Université d'ALBANY EST – RENSSELAER – USA
- Cindy SAGE – Membre titulaire de la BS
Travaux publiés cités en référence ………………………………...…49
POUR TELECHARGER LE TEXTE (rapport intégral en anglais) :
A Rationale for a Biologically-based Public Exposure Standard for Electromagnetic Fields (ELF and RF)
mardi 17 juin 2008
The Hedgehog (Hh) signaling pathway is a key regulator of both embryonic development and homeostasis of adult tissues
Macintosh) and select the option to save the file to disk.
The Hedgehog (Hh) signaling pathway is a key regulator of both embryonic development and homeostasis of adult tissues, including thymus and blood. In the thymus, Hh signals for differentiation, survival and proliferation in the early stages of T cell development, before TCR gene rearrangement. Our recent data has shown that Hh signaling also modulates T cell receptor (TCR) signal strength in more mature T lineage cells. We showed that constitutive activation of the Hh pathway in thymocytes (by transgenic expression of the transcriptional activator form of Gli2) decreased TCR signal strength with profound consequences for the thymus - allowing self-reactive T cells to escape deletion and altering T cell CD4/CD8 lineage decisions. In contrast, in the Sonic Hh deficient thymus, TCR signaling was increased, again influencing both TCR repertoire selection and CD4/8 lineage commitment. In peripheral T cells, the transcriptional changes induced by activation of the Hh signaling pathway lead to reduced T cell activation. Hh signaling also attenuated ERK phosphorylation and proliferation in mature T cells on TCR ligation. Modulation of TCR signal strength by Hh pathway activation has importance for immunity as the presence or absence of Hh in the environment in which a T cell is activated would shape the immune response.
Authors
Nicola J. Rowbotham
UCL Institute of Child Health; London UK
The Hedgehog (Hh) signaling pathway is a key regulator of both embryonic development and homeostasis of adult tissues, including thymus and blood. In the thymus, Hh signals for differentiation, survival and proliferation in the early stages of T cell development, before TCR gene rearrangement. Our recent data has shown that Hh signaling also modulates T cell receptor (TCR) signal strength in more mature T lineage cells. We showed that constitutive activation of the Hh pathway in thymocytes (by transgenic expression of the transcriptional activator form of Gli2) decreased TCR signal strength with profound consequences for the thymus - allowing self-reactive T cells to escape deletion and altering T cell CD4/CD8 lineage decisions. In contrast, in the Sonic Hh deficient thymus, TCR signaling was increased, again influencing both TCR repertoire selection and CD4/8 lineage commitment. In peripheral T cells, the transcriptional changes induced by activation of the Hh signaling pathway lead to reduced T cell activation. Hh signaling also attenuated ERK phosphorylation and proliferation in mature T cells on TCR ligation. Modulation of TCR signal strength by Hh pathway activation has importance for immunity as the presence or absence of Hh in the environment in which a T cell is activated would shape the immune response.
Authors
Nicola J. Rowbotham
UCL Institute of Child Health; London UK
Pregnancy As a Tumor
Supporting the Hypothesis of Pregnancy As a Tumor: Survivin Is Upregulated in Normal Pregnant Mice and Participates in Human Trophoblast Proliferation
Abstract
Problem Survivin, a tumor-promoting antiapoptotic molecule, is expressed in the human placenta. Here, we analyzed its expression during normal and pathological murine pregnancy and investigated its participation in human first trimester trophoblast cell survival and proliferation.
Method of study We first analyzed the expression of survivin on the mRNA and protein level at the fetal–maternal interface of normal pregnant (CBA/J × BALB/c) and abortion-prone (CBA/J × DBA/2J) mice at different pregnancy stages by RT-PCR and immunohistochemistry. We also evaluated apoptosis in murine trophoblasts in both mating combinations by TUNEL technique. Functional studies were carried out by knockdown survivin by means of siRNA methodology in two human first trimester trophoblast cell lines [Swan.71 (Sw.71) and HTR8 (H8)].
Results We observed a peak in mRNA levels on day 5 and a peak of protein levels on day 8 of pregnancy in both combinations. The level of survivin in animals from the abortion-prone group was decreased compared with normal pregnant mice on day 8, which was accompanied by elevated apoptosis rates. In later pregnancy stages (days 10 and 14), survivin levels decreased to levels comparable to those observed right after fecundation in both groups. Transfection of human first trimester cell lines (H8 and Sw.71) with siRNA targeting the survivin gene led to a 76–82% reduction of its expression leading to reduced trophoblast cell viability and proliferation.
Conclusion Our findings suggest an important role of survivin to promote trophoblast cell survival and proliferation during placentation, thus maintaining pregnancy. The pregnancy-associated expression of a cancer molecule such as survivin supports the ‘pseudo-malignancy’ hypothesis of pregnancy. Our data may contribute to the better understanding of trophoblast cell development during implantation and placentation
Abstract
Problem Survivin, a tumor-promoting antiapoptotic molecule, is expressed in the human placenta. Here, we analyzed its expression during normal and pathological murine pregnancy and investigated its participation in human first trimester trophoblast cell survival and proliferation.
Method of study We first analyzed the expression of survivin on the mRNA and protein level at the fetal–maternal interface of normal pregnant (CBA/J × BALB/c) and abortion-prone (CBA/J × DBA/2J) mice at different pregnancy stages by RT-PCR and immunohistochemistry. We also evaluated apoptosis in murine trophoblasts in both mating combinations by TUNEL technique. Functional studies were carried out by knockdown survivin by means of siRNA methodology in two human first trimester trophoblast cell lines [Swan.71 (Sw.71) and HTR8 (H8)].
Results We observed a peak in mRNA levels on day 5 and a peak of protein levels on day 8 of pregnancy in both combinations. The level of survivin in animals from the abortion-prone group was decreased compared with normal pregnant mice on day 8, which was accompanied by elevated apoptosis rates. In later pregnancy stages (days 10 and 14), survivin levels decreased to levels comparable to those observed right after fecundation in both groups. Transfection of human first trimester cell lines (H8 and Sw.71) with siRNA targeting the survivin gene led to a 76–82% reduction of its expression leading to reduced trophoblast cell viability and proliferation.
Conclusion Our findings suggest an important role of survivin to promote trophoblast cell survival and proliferation during placentation, thus maintaining pregnancy. The pregnancy-associated expression of a cancer molecule such as survivin supports the ‘pseudo-malignancy’ hypothesis of pregnancy. Our data may contribute to the better understanding of trophoblast cell development during implantation and placentation
DAF-16-Dependent Suppression of Immunity During Reproduction in Caenorhabditis elegans
Genetics. 2008 February; 178(2): 903–918.
doi: 10.1534/genetics.107.083923. PMCID: PMC2248360
Copyright © 2008 by the Genetics Society of America
DAF-16-Dependent Suppression of Immunity During Reproduction in Caenorhabditis elegans
Sachiko Miyata
To further understand how the nematode Caenorhabditis elegans defends itself against pathogen attack, we analyzed enhanced pathogen resistance (epr) mutants obtained from a forward genetic screen. We also examined several well-characterized sterile mutants that exhibit an Epr phenotype. We found that sterility and pathogen resistance are highly correlated and that resistance in both epr and sterile mutants is dependent on DAF-16 activity.
Our data indicate that a DAF-16-dependent signaling pathway distinct from previously described pathways is involved in the activation of genes that confer resistance to bacterial pathogens. The timing of DAF-16-dependent gene activation in sterile mutants coincides with the onset of embryonic development in wild-type animals, suggesting that signals from developing embryos normally downregulate the immune response.
doi: 10.1534/genetics.107.083923. PMCID: PMC2248360
Copyright © 2008 by the Genetics Society of America
DAF-16-Dependent Suppression of Immunity During Reproduction in Caenorhabditis elegans
Sachiko Miyata
To further understand how the nematode Caenorhabditis elegans defends itself against pathogen attack, we analyzed enhanced pathogen resistance (epr) mutants obtained from a forward genetic screen. We also examined several well-characterized sterile mutants that exhibit an Epr phenotype. We found that sterility and pathogen resistance are highly correlated and that resistance in both epr and sterile mutants is dependent on DAF-16 activity.
Our data indicate that a DAF-16-dependent signaling pathway distinct from previously described pathways is involved in the activation of genes that confer resistance to bacterial pathogens. The timing of DAF-16-dependent gene activation in sterile mutants coincides with the onset of embryonic development in wild-type animals, suggesting that signals from developing embryos normally downregulate the immune response.
Sarkozy prépare la France à une guerre contre l'Iran
Sarkozy prépare-t-il la France à une guerre contre l'Iran?
http://globe.blogs.nouvelobs.com/archive/2008/06/17/sarkozy-prepare-t-il-la-france-a-une-guerre-contre-l-iran.html
Nicolas Sarkozy a prononcé aujourd'hui un "discours fondateur" (ce sont ses mots) sur la Défense.
Il a annoncé une réforme majeure - et nécessaire à bien des égards - de notre outil militaire.
On retiendra bien sûr l'accent mis, à juste titre, sur les services secrets, le renseignement spatial, la réduction des effectifs et la modernisation des équipements.
On retiendra aussi que le président ne veut pas "assumer" la décision de construire un second porte-avions (décision qu'il ne juge pas urgente, on ne sait pourquoi).
On retiendra enfin son plaidoyer pour l'Otan et l'Europe de la Défense, Nicolas Sarkozy promettant qu'une réintégration de la France dans le commandement intégré de l'Alliance atlantique ne se fera que "si au préalable il y a un progrès de l'Europe de la Défense"(le président se gardant bien de préciser quel progrès il attend, surtout après le rejet irlandais du traité de Lisbonne qui devait justement être le cadre institutionnel de cette relance.)
Mais il y a un point qui passera peut-être inaperçu et qui me semble pourtant mériter une attention toute particulière.
C'est ce que Nicolas Sarkozy a dit et ce qu'il a sous-entendu concernant l'Iran.
Le chef de l'Etat a, en effet, insisté sur la nécessité de "recentrer" notre présence militaire à l'étranger "sur nos zones d'intérêt stratégique"et, à ce propos, il a mentionné les accords qu'il a passés avec les Émirats Arabes Unis et donc l'ouverture de la base française à Abou Dhabi, située en face des côtes iraniennes.
Et quelques minutes plus tard, il a justement parlé de la République islamique en disant que "la crise iranienne était la première menace qui pèse sur le monde".
En fait, l'Iran est le seul pays étranger (en dehors de l'allié américain) que le chef de l'Etat a mentionné au cours de son discours sur la défense - le seul.
S'agit-il d'une simple gesticulation visant à faire pression sur Téhéran au moment où les leaders iraniens viennent, une nouvelle fois, de refuser une proposition des Six?
Ou est-ce déjà une préparation psychologique de l'opinion française à d'éventuelles frappes américaines et/ou israéliennes que la France soutiendrait en se chargeant, par exemple, de contrôler une partie du Golfe persique à partir notamment de sa base d'Abou Dhabi?
Intensive nutrition and lifestyle changes may modulate gene expression
Proc. Natl. Acad. Sci. USA, 10.1073/pnas.0803080105
Changes in prostate gene expression in men undergoing an intensive nutrition and lifestyle intervention
Dean Ornish*, Mark Jesus M. Magbanua, Gerdi Weidner*, Vivian Weinberg¶, Colleen Kemp*, Christopher Green, Michael D. Mattie, Ruth Marlin*, Jeff Simko||, Katsuto Shinohara, Christopher M. Haqq, and Peter R. Carroll
Department of Urology, The Helen Diller Family Comprehensive Cancer Center, and ||Department of Pathology, University of California, 2340 Sutter Street, San Francisco, CA 94115; *Preventive Medicine Research Institute, 900 Bridgeway, Sausalito, CA 94965; Department of Medicine, School of Medicine, University of California, 505 Parnassus Avenue, San Francisco, CA 94143; and ¶Biostatistics Core, The Helen Diller Family Comprehensive Cancer Center, University of California, 513 Parnassus Avenue, Box 0127, San Francisco, CA 94143
Communicated by J. Craig Venter, The J. Craig Venter Institute, Rockville, MD, April 2, 2008 (received for review February 13,2008)
Abstract
Epidemiological and prospective studies indicate that comprehensive lifestyle changes may modify the progression of prostate cancer.
However, the molecular mechanisms by which improvements in diet and lifestyle might affect the prostate microenvironment are poorly understood.
We conducted a pilot study to examine changes in prostate gene expression in a unique population of men with low-risk prostate cancer who declined immediate surgery, hormonal therapy, or radiation and participated in an intensive nutrition and lifestyle intervention while undergoing careful surveillance for tumor progression.
Consistent with previous studies, significant improvements in weight, abdominal obesity, blood pressure, and lipid profile were observed (all P < 0.05), and surveillance of low-risk patients was safe.
Gene expression profiles were obtained from 30 participants, pairing RNA samples from control prostate needle biopsy taken before intervention to RNA from the same patient's 3-month postintervention biopsy. Quantitative real-time PCR was used to validate array observations for selected transcripts.
Two-class paired analysis of global gene expression using significance analysis of microarrays detected 48 up-regulated and 453 down-regulated transcripts after the intervention.
Pathway analysis identified significant modulation of biological processes that have critical roles in tumorigenesis, including protein metabolism and modification, intracellular protein traffic, and protein phosphorylation (all P < 0.05).
Intensive nutrition and lifestyle changes may modulate gene expression in the prostate.
Understanding the prostate molecular response to comprehensive lifestyle changes may strengthen efforts to develop effective prevention and treatment. Larger clinical trials are warranted to confirm the results of this pilot study.
Changes in prostate gene expression in men undergoing an intensive nutrition and lifestyle intervention
Dean Ornish*, Mark Jesus M. Magbanua, Gerdi Weidner*, Vivian Weinberg¶, Colleen Kemp*, Christopher Green, Michael D. Mattie, Ruth Marlin*, Jeff Simko||, Katsuto Shinohara, Christopher M. Haqq, and Peter R. Carroll
Department of Urology, The Helen Diller Family Comprehensive Cancer Center, and ||Department of Pathology, University of California, 2340 Sutter Street, San Francisco, CA 94115; *Preventive Medicine Research Institute, 900 Bridgeway, Sausalito, CA 94965; Department of Medicine, School of Medicine, University of California, 505 Parnassus Avenue, San Francisco, CA 94143; and ¶Biostatistics Core, The Helen Diller Family Comprehensive Cancer Center, University of California, 513 Parnassus Avenue, Box 0127, San Francisco, CA 94143
Communicated by J. Craig Venter, The J. Craig Venter Institute, Rockville, MD, April 2, 2008 (received for review February 13,2008)
Abstract
Epidemiological and prospective studies indicate that comprehensive lifestyle changes may modify the progression of prostate cancer.
However, the molecular mechanisms by which improvements in diet and lifestyle might affect the prostate microenvironment are poorly understood.
We conducted a pilot study to examine changes in prostate gene expression in a unique population of men with low-risk prostate cancer who declined immediate surgery, hormonal therapy, or radiation and participated in an intensive nutrition and lifestyle intervention while undergoing careful surveillance for tumor progression.
Consistent with previous studies, significant improvements in weight, abdominal obesity, blood pressure, and lipid profile were observed (all P < 0.05), and surveillance of low-risk patients was safe.
Gene expression profiles were obtained from 30 participants, pairing RNA samples from control prostate needle biopsy taken before intervention to RNA from the same patient's 3-month postintervention biopsy. Quantitative real-time PCR was used to validate array observations for selected transcripts.
Two-class paired analysis of global gene expression using significance analysis of microarrays detected 48 up-regulated and 453 down-regulated transcripts after the intervention.
Pathway analysis identified significant modulation of biological processes that have critical roles in tumorigenesis, including protein metabolism and modification, intracellular protein traffic, and protein phosphorylation (all P < 0.05).
Intensive nutrition and lifestyle changes may modulate gene expression in the prostate.
Understanding the prostate molecular response to comprehensive lifestyle changes may strengthen efforts to develop effective prevention and treatment. Larger clinical trials are warranted to confirm the results of this pilot study.
lundi 16 juin 2008
DANGER : INTERNET RISQUE DE DEVENIR COMME LA TELE
Ce petit film est probablement le meilleur résumé de la question de la “Net Neutrality” et comment la question de l’investissement financier nécessaire pour faire fonctionner Internet risque de mettre en péril l’existence même du réseau.
Ce n’est pas nouveau, comme Lawrence Lessig le démontre bien : au début de la presse d’imprimerie, le coût d’une presse était l’équivalent de 8 000 Euros d’aujourd’hui. 100 ans plus tard, pour imprimer un journal, il fallait déjà sortir 2 millions d’Euros. Cela réduisit déjà la possibilité pour les gens de s’exprimer… 100 ans plus tard la même chose se produisit avec la radio.
Aujourd’hui les opérateurs télécoms disent “les tuyeaux sont à nous, c’est nous qui décideons ce qui va circuler dedans”… mais contrairement à la télé ou la radio, ou la majorité des contenus sont fabriqués par les grands groupes, sur Internet plus de 60% des contenus sont fabriqués par les usagers eux mêmes.
Pour les opérateurs, Internet doit devenir comme la télé…
DANGER : INTERNET RISQUE DE DEVENIR COMME LA TELE
Ce n’est pas nouveau, comme Lawrence Lessig le démontre bien : au début de la presse d’imprimerie, le coût d’une presse était l’équivalent de 8 000 Euros d’aujourd’hui. 100 ans plus tard, pour imprimer un journal, il fallait déjà sortir 2 millions d’Euros. Cela réduisit déjà la possibilité pour les gens de s’exprimer… 100 ans plus tard la même chose se produisit avec la radio.
Aujourd’hui les opérateurs télécoms disent “les tuyeaux sont à nous, c’est nous qui décideons ce qui va circuler dedans”… mais contrairement à la télé ou la radio, ou la majorité des contenus sont fabriqués par les grands groupes, sur Internet plus de 60% des contenus sont fabriqués par les usagers eux mêmes.
Pour les opérateurs, Internet doit devenir comme la télé…
DANGER : INTERNET RISQUE DE DEVENIR COMME LA TELE
vendredi 13 juin 2008
one of the most beautifully illuminated manuscripts in the world : the Book of Kells
Book of Kells was written around the year 800 AD and is one of the most beautifully illuminated manuscripts in the world. It contains the four gospels, preceded by prefaces, summaries, and canon tables or concordances of gospel passages. It is written on vellum and contains a Latin text of the Gospels in insular majuscule script accompanied by magnificent and intricate whole pages of decoration with smaller painted decorations appearing throughout the text. The manuscript was given to Trinity College in the 17th century and since 1953 has been bound in four volumes. It has been on display in the Old Library since the 19th century. Two volumes can normally be seen, one opened to display a major decorated page, and one to show two pages of script
'Dead' patient comes around as organs are about to be removed
France may have to reconsider its medical definition of death after a heart-attack victim came alive in the operating theatre as doctors were about to remove his organs for transplant.
The patient, whose identity has not been revealed, recovered after a long period in intensive care and is now able to walk and talk.
The 45-year-old man owes his life to the fact that surgeons authorised to remove organs for transplant operations were not immediately available. Under experimental rules adopted in France last year, to make more organ transplants possible, the man had already reached the point where he could be officially regarded as dead. Similar rules – allowing the removal of organs when a patient's heart has stopped and fails to respond to prolonged massage – already apply in several other European countries, including Britain.
The case occurred at the Pitié-Salpêtriere hospital in Paris in January but was not revealed at the time. The organisation that runs state-owned hospitals in the Paris area – Assistance Publique-Hôpitaux de Paris (AP-HP) – referred the case to its ethical committee on transplants. A summary of the committee's debate, which came to no firm conclusion, has now been published on the AP-HP website. "This situation [illustrates] the questions that remain in reanimation ... and what criteria can be used to determine that a reanimation has failed," says the report.
The ethical questions raised are complex, as the committee acknowledges that doctors – and the state – have an obligation to the 13,000 people waiting for transplanted organs in France. Last year 231 of these patients died because organs did not become available. It was for this reason that France introduced experimental rules allowing the removal of organs in nine hospitals from so-called "stopped heart" patients.
The 45-year-old at the centre of the controversy collapsed close to the La Pitié-Salpêtriere hospital. Efforts were made to revive him at the scene, and more elaborate procedures continued at the hospital for 90 minutes. As surgeons were preparing to remove his vital organs, the man began to breathe unaided. His pupils moved and he showed signs of pain. His heart started to beat again. After several weeks during which he was gravely ill, the man can now walk and talk. He has yet to be told that doctors were ready to remove his organs.
Otherdoctors have seen similar incidents, according to the ethics committee report. "During the meeting, other reanimators ... spoke of situations in which a person whom everyone was sure had died in fact survived after reanimation efforts that went on much longer than usual," the report said. "Participants conceded that these were exceptional cases, but ones that were nevertheless seen in the course of a career."
Le Monde said doctors had feared the new transplant rules would confront them with cases of this kind. They believe the existing rules are imprecise and could undermine public support for the removal of organs for transplant. They are pushing for the issue to be discussed as part of a consultation next year on a proposed, new law on medical ethics.
Professor Alain Tenaillon, the organ transplant specialist at the French government's agency of bio-medicine, told Le Monde: "All the specialist literature suggests that anyone whose heart has stopped and has been massaged correctly for more than 30 minutes, is probably brain dead. But we have to accept that there are exceptions.... There are no absolute rules in this area."
http://www.independent.co.uk/life-style/health-and-wellbeing/health-news/dead-patient-comes-around-as--organs-are-about-to-be-removed-845140.html
The patient, whose identity has not been revealed, recovered after a long period in intensive care and is now able to walk and talk.
The 45-year-old man owes his life to the fact that surgeons authorised to remove organs for transplant operations were not immediately available. Under experimental rules adopted in France last year, to make more organ transplants possible, the man had already reached the point where he could be officially regarded as dead. Similar rules – allowing the removal of organs when a patient's heart has stopped and fails to respond to prolonged massage – already apply in several other European countries, including Britain.
The case occurred at the Pitié-Salpêtriere hospital in Paris in January but was not revealed at the time. The organisation that runs state-owned hospitals in the Paris area – Assistance Publique-Hôpitaux de Paris (AP-HP) – referred the case to its ethical committee on transplants. A summary of the committee's debate, which came to no firm conclusion, has now been published on the AP-HP website. "This situation [illustrates] the questions that remain in reanimation ... and what criteria can be used to determine that a reanimation has failed," says the report.
The ethical questions raised are complex, as the committee acknowledges that doctors – and the state – have an obligation to the 13,000 people waiting for transplanted organs in France. Last year 231 of these patients died because organs did not become available. It was for this reason that France introduced experimental rules allowing the removal of organs in nine hospitals from so-called "stopped heart" patients.
The 45-year-old at the centre of the controversy collapsed close to the La Pitié-Salpêtriere hospital. Efforts were made to revive him at the scene, and more elaborate procedures continued at the hospital for 90 minutes. As surgeons were preparing to remove his vital organs, the man began to breathe unaided. His pupils moved and he showed signs of pain. His heart started to beat again. After several weeks during which he was gravely ill, the man can now walk and talk. He has yet to be told that doctors were ready to remove his organs.
Otherdoctors have seen similar incidents, according to the ethics committee report. "During the meeting, other reanimators ... spoke of situations in which a person whom everyone was sure had died in fact survived after reanimation efforts that went on much longer than usual," the report said. "Participants conceded that these were exceptional cases, but ones that were nevertheless seen in the course of a career."
Le Monde said doctors had feared the new transplant rules would confront them with cases of this kind. They believe the existing rules are imprecise and could undermine public support for the removal of organs for transplant. They are pushing for the issue to be discussed as part of a consultation next year on a proposed, new law on medical ethics.
Professor Alain Tenaillon, the organ transplant specialist at the French government's agency of bio-medicine, told Le Monde: "All the specialist literature suggests that anyone whose heart has stopped and has been massaged correctly for more than 30 minutes, is probably brain dead. But we have to accept that there are exceptions.... There are no absolute rules in this area."
http://www.independent.co.uk/life-style/health-and-wellbeing/health-news/dead-patient-comes-around-as--organs-are-about-to-be-removed-845140.html
Controversial World War II book questions 'just war' : Human Smoke: The Beginnings of World War II, the End of Civilization by Nicholson Baker
SOUTH BERWICK, Maine, USA, Nicholson Baker's nonfiction work about World War II has generated controversy.Even the staunchest opponents of the wars in Vietnam and Iraq are loath to take issue with World War II, the quintessential conflict between good and evil that became the model of a morally just war.
So it's no surprise that novelist Nicholson Baker's latest venture into nonfiction, "Human Smoke," has stirred up strong feelings. After all, he questions the popular notion of the just war and indicates that Winston Churchill and Franklin Roosevelt share blame with Adolf Hitler in setting the stage for the deadliest and most destructive war in history.
Baker makes his case through hundreds of brief vignettes culled from newspapers, diaries and secondary sources that are presented chronologically and without context or commentary by the author. The book ends on December 31, 1941, as the world plunges into the abyss.
In a two-page "afterword," Baker dedicates the book to pacifists who risked public scorn and imprisonment by fighting to stave off the war.
Outraged by the invasion of Iraq, Baker said he was familiar with arguments that some wars had to be fought and that World War II is the premier example.
"If this is the war that everyone holds up as the benchmark of a morally justified war, let's look very closely at how it began, let's find out what happened, in what order and where the moments were that things could have turned out differently.
"Let's ask the question, 'Was it a good war?' " he said in an interview at his 18th-century farmhouse in this New Hampshire border town where he and his family have lived for the past decade.
Exploring the origins of World War II may seem something of a reach for an unconventional author known for quirky novels such as "Vox," which details a phone sex conversation and became a footnote to history after it was learned that Monica Lewinsky had given a copy to President Bill Clinton. Another novel, "The Mezzanine," explores the thoughts of an office worker who rides an escalator during his lunch hour.
Baker has written articles in The New Yorker, ranging from the history of the fingernail clipper to the workings of a movie projector, but his best-known shift to nonfiction was the 2001 "Double Fold," which lamented the destruction of newspaper archives and their replacement by microfilm.
It was while tending the British Library newspaper collection that he rescued from the shredder that Baker began reading about "the horrible period" that led to World War II and prompted him to dig deeper and try "to make some sense" of the situation.
Baker said he was surprised and shocked at the way Churchill responded to Hitler's attacks on Poland and other neighboring states by launching a relentless bombing campaign against German cities as well as a blockade that was designed to starve the enemy into submission.
"He was acting like a bloodthirsty maniac during that period. That has to go back on the record in all of its unpleasantness. We can't learn from a hero like that. It's a mistake to say that because Hitler was bad, we have to clean up the image of Churchill. Churchill was also bad," Baker said.
Baker maintains that Churchill's bellicose actions and Roosevelt's eagerness to supply Britain with ships and planes served only to prop up Hitler's standing with Germans and strengthen his hold on the country.
"It was the war -- the long, slow war of bombing and blockade -- that fundamentally helped to keep Hitler in power," he said. "The fact that the country was attacked night after night in this way released a massive antipathy to the British."
The people in the book whom Baker looks up to include Mohandas Gandhi, the apostle of nonviolence; Herbert Hoover, who opposed the British blockade; and a handful of lesser-known pacifists who spoke out against the run up to war.
Tall and lean, with a full but neatly trimmed white beard, the 51-year-old Baker does not regard himself as "a war-minded person," but neither does he claim to be "an absolute pacifist." He is sympathetic to the Quaker tradition of nonviolence, having had Quaker forebears and having gone to Haverford College, which was founded by Quakers.
"Human Smoke," which draws its title from a description of the ashes at Auschwitz, is not meant to be a comprehensive history. Rather, he said, "it's just one journey through the thicket of events," one that captures the anguish of the period and puts human faces on those caught up in it.
The book slices and dices the years that led to war into hundreds of little anecdotes rather than a single sweeping narrative. Baker presents the facts in a detached, journalistic manner that belies his underlying passion and leaves it to the reader to sort out contradictions and infer the broader picture.
Reviews, Baker noted, have ranged from "extremely positive" to "ferociously negative." In The New York Times, William Grimes vilified "Human Smoke" as a "self-important, hand-wringing, moral mess of a book." But Colm Toibin, in the newspaper's Sunday Book Review, called it "riveting and fascinating" and "a serious and conscientious contribution to the debate about pacifism."
Among the skeptics was Holocaust scholar Michael Berenbaum, who helped oversee the creation of the United States Holocaust Memorial Museum.
"If there ever was a war that was worth fighting it was World War II, and there is no evidence that I know of whatsoever that Hitler would have responded to passivity except to regard that as empowering him to expand," Berenbaum said. "Hitler could only be stopped by force."
Human Smoke: The Beginnings of World War II, the End of Civilization by Nicholson Baker.
jeudi 12 juin 2008
Deaf-1 immunity
Defective Neural Tube Closure and Anteroposterior Patterning in Mice Lacking the LIM Protein LMO4 or Its Interacting Partner Deaf-1
Kyungmin Hahm, Eleanor Y. M. Sum, Yuko Fujiwara, Geoffrey J. Lindeman, Jane E. Visvader, and Stuart H. Orkin
Mol. Cell. Biol., Mar 2004; 24: 2074 - 2082.
LMO4 belongs to a family of transcriptional regulators that comprises two zinc-binding LIM domains.
LIM-only (LMO) proteins appear to function as docking sites for other factors, leading to the assembly of multiprotein complexes.
The transcription factor Deaf-1/NUDR has been identified as one partner protein of LMO4.
We have disrupted the Lmo4 and Deaf-1 genes in mice to define their biological function in vivo.
All Lmo4 mutants died shortly after birth and showed defects within the presphenoid bone, with 50% of mice also exhibiting exencephaly.
Homeotic transformations were observed in Lmo4-null embryos and newborn mice, but with incomplete penetrance. These included skeletal defects in cervical vertebrae and the rib cage. Furthermore, fusions of cranial nerves IX and X and defects in cranial nerve V were apparent in some Lmo4-/- and Lmo4+/- mice.
Remarkably, Deaf-1 mutants displayed phenotypic abnormalities similar to those observed in Lmo4 mutants.
These included exencephaly, transformation of cervical segments, and rib cage abnormalities. In contrast to Lmo4 nullizygous mice, nonexencephalic Deaf-1 mutants remained healthy. No defects in the sphenoid bone or cranial nerves were apparent. Thus, Lmo4 and Deaf-1 mutant mice exhibit overlapping as well as distinct phenotypes.
Our data indicate an important role for these two transcriptional regulators in pathways affecting neural tube closure and skeletal patterning, most likely reflecting their presence in a functional complex in vivo.
DEAF-1 regulates immunity gene expression in Drosophila
Darien E. Reed*, Xinhua M. Huang, James A. Wohlschlegel, Michael S. Levine,, and Kate Senger,¶
*Helen Diller Family Comprehensive Cancer Center and Cancer Research Institute, University of California, San Francisco, CA 94115-0128; Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, CA 90095-1737; Department of Molecular and Cell Biology, Division of Genetics, Genomics, and Development, Center for Integrative Genomics, University of California, Berkeley, CA 94720-3200; and ¶Department of Immunology Discovery, Genentech, South San Francisco, CA 94080-4990
Contributed by Michael S. Levine, March 31, 2008 (sent for review February 2, 2008)
Abstract
Immunity genes are activated in the Drosophila fat body by Rel and GATA transcription factors.
Here, we present evidence that an additional regulatory factor, deformed epidermal autoregulatory factor-1 (DEAF-1), also contributes to the immune response and is specifically important for the induction of two genes encoding antimicrobial peptides, Metchnikowin (Mtk) and Drosomycin (Drs).
The systematic mutagenesis of a minimal Mtk 5' enhancer identified a sequence motif essential for both a response to LPS preparations in S2 cells and activation in the larval fat body in response to bacterial infection.
Using affinity chromatography coupled to multidimensional protein identification technology (MudPIT), we identified DEAF-1 as a candidate regulator.
DEAF-1 activates the expression of Mtk and Drs promoter-luciferase fusion genes in S2cells.
SELEX assays and footprinting data indicate that DEAF-1 binds to and activates Mtk and Drs regulatory DNAs via a TTCGGBT motif.
The insertion of this motif into the Diptericin (Dpt) regulatory region confers DEAF-1 responsiveness to this normally DEAF-1-independent enhancer.
The coexpression of DEAF-1 with Dorsal, Dif, and Relish results in the synergistic activation of transcription.
We propose that DEAF-1 is a regulator of Drosophila immunity.
J Biol Chem, Vol. 273, Issue 22, 13746-13752, May 29, 1998
Overexpression of a Novel Xenopus Rel mRNA Gene Induces Tumors in Early Embryos
Saoshan Yang, Ann Lockwood, Peter Hollett, Rebecca Ford, and Kenneth Kao
From the Terry Fox Cancer Research Laboratory, Division of Basic Medical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland A1B 3V6, Canada
The Rel family of transcriptional activators form a large diverse group of proteins that are involved in the activation of genes involved in immunity, development, apoptosis and cancer. So far, none of the rel genes cloned in mammals appear to be required for embryonic development. We have cloned and characterized a cDNA from an embryonic cDNA library that encodes a novel Xenopus Rel protein, called Xrel3. Xrel3 is a member of the cRel subfamily and is most closely related to but distinct from other Xenopus Rel members. The expression of Xrel3 mRNA was investigated using Northern analysis, RNase protection assay, reverse transcriptase-linked polymerase chain reaction and in situ hybridization. Messages are present maternally and are slightly enriched in the equatorial region of the blastula stage embryo. At gastrulation, the accumulation of Xrel3 messages declines to undetectable levels but then increases after neurulation. In situ RNA hybridization was used to determine the spatial location of Xrel3 messenger RNA in embryos. Messages are localized to the developing forebrain, dorsal mid-hindbrain region, the inner ear primordium, or otocyst, and in the notochord. Overexpression by microinjection of Xrel3 RNA induced tumors in the developing embryo that appeared after gastrulation. The location of the tumors depended on the location of the injection site. These results suggest that Xrel3 might have a generalized role in regulation of cell differentiation in the embryo
Médecine/Science | Décembre 2005 | Volume 21 | n° 12
Les cellules souches embryonnaires : du développement myocardique à la médecine régénératrice
Embryonic stem cells to study early myocardial development and potential regenerative medicine
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Integrative and Comparative Biology 2003 43(2):293-299; doi:10.1093/icb/43.2.293
© 2003 by The Society for Integrative and Comparative Biology
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Origins and Evolutionary Relationships Between the Innate and Adaptive Arms of Immune Systems1
Christopher J. Bayne2,1
1 Department of Zoology, Oregon State University, Corvallis, Oregon 97331-2914
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Long before vertebrates first appeared, protists, plants and animals had evolved diverse, effective systems of innate immunity. Ancestors of the vertebrates utilized components of the complement system, protease-inhibitors, metal-binding proteins, carbohydrate-binding proteins and other plasma-born molecules as humoral agents of defense. In these same animals, immunocytes endowed with a repertoire of defensive behaviors expressed Toll-like receptors. They made NADPH oxidase, superoxide dismutase and other respiratory burst enzymes to produce toxic oxygen radicals, and nitric oxide synthase to produce nitric oxide. Antimicrobial peptides and lytic enzymes were in their armory. Immune responses were orchestrated by cytokines. Furthermore, genes within the immunoglobulin superfamily were expressed to meet a variety of needs possibly including defense. However, recombination activating genes played no role. With the acquisition of one or more transposases and the resulting capacity to generate diverse receptors from immunoglobulin gene fragments, the adaptive (lymphoid) arm of the immune system was born. This may have coincided with the elaboration of the neural crest. Naturally, the role of the adaptive arm was initially subservient to the defensive functions of the pre-existing innate arm. The strong selective advantages that stemmed from having "sharp-shooters" (cells making antigen-specific receptors) on the defense team ensured their retention. Refined through evolution, adaptive immunity, even in mammals, remains dependent upon cells of the innate series (e.g., dendritic cells) for signals driving their functional maturation. This paper calls for some fresh thinking leading to a clearer vision of the origins and co-evolution of the two arms of modern immune systems, and suggests a possible neural origin for the adaptive immune system.
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With few exceptions, the study of immunology has—for the past several decades at least—been predominantly the study of lymphoid biology. And what a fascinating story it has turned out to be: each individual of a species will acquire—de novo—receptors able to recognize with exquisite specificity a huge variety of foreign antigens. For each antigen that is subsequently re-encountered, lymphocytes recognizing the antigen will remember the previous encounter and respond more effectively.
In the 1970s, the influential comparative immunologist Bill Hildemann catalyzed a re-examination of the concepts of immuno-phylogeny (Hildemann et al., 1981). Hildemann appreciated that, in pioneering studies of inflammation and phagocytosis, Eli Metchnikof, the father of immunology, had made use of rose thorns, water fleas and starfish larvae. Attracted by the opportunity to "do immunology" in coral reefs, Hildemann focused the mind of a classical immunogeneticist first on experiments of Nature and later on laboratory-based "grafting" experiments with corals and sponges (Hildemann et al., 1979).
Further illustrating the prodigious fruitfulness that can result when a mind that is well informed in one area engages another, microbiologist Hans Boman in Sweden simultaneously initiated studies of the basis for acquired resistance to bacterial pathogens in insects (Boman, 1998). That work catalyzed the discovery of antimicrobial peptides throughout phylogeny, and eventually the discovery of immune functions for Toll and Toll-like receptors, and the NFB/Rel system of transcriptional activators (Medzhitov and Janeway, 2000a). Starting in the mid-20th century and continuing to the present, additional free-thinking individualists, more interested in basic biology than in joining the mainstream, have sought to discover non-immunoglobulin based mechanisms of defense. This relatively small cadre of scientists have contributed significantly to the refinement of ideas on the evolution of immunity, through efforts to understand how animals lacking lymphoid systems manage to survive in a world replete with both micro- and macro-pathogens and parasites (see as an example Beck et al., 2001).
As is now generally appreciated, the ability to recombine germline-encoded gene segments and to synthesize numerous unique antigen-recognizing receptor proteins encoded by the novel reading frames was acquired about 430 million years ago in organisms resembling primitive jawed fishes. Genes encoding members of the immunoglobulin superfamily had been expressed for hundreds of millions of years prior to that time, and their functions are thought to have been predominantly though not exclusively non-defensive (e.g., Aurelio et al., 2002). Recent thinking envisages the lateral transfer of a prokaryotic transposase with an aptitude to create recombinants out of pre-existing immunoglobulin gene segments (Agrawal, 2000). This event spawned the now inappropriate term3 "adaptive immune system."
Seduced by the impressive sophistication (or is it mere complexity?) of lymphoid biology in modern birds and mammals, some immunologists have tended to view all components of innate immunity as subservient to the adaptive arm of the immune system. An influential voice encouraging a change in perspective has been that of Charles Janeway (2001). The present paper contributes to the call for reconsideration by examining the immune landscape around the time when the transposases supposedly invaded and quickly evolved into the recombination activating genes (RAG 1 and 2) in early gnathostomes (Flajnik and Kasahara, 2001). In doing this, it crystallizes the tantalizing notion that the adaptive arm of the immune system may be an evolutionary offshoot of the nervous system.
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Being immunocompetent means being able to defend oneself against potentially damaging microbes and parasites. And because neoplasia can be fatal, guarding against it has come to be seen as a second criterion of immunocompetence. This capacity to protect oneself requires both a means of surveillance (detection) and the means to neutralize the threat. Both capabilities appeared very early in the history of the evolution of life. Navigating away from life-threatening conditions and towards nutrients requires discriminating senses and appropriate behaviors that are seen even in prokaryotes. Among unicellular protists (eukaryotes), propagation depends on the ability to discriminate between different mating types, made possible by the presence of specific markers and recognition receptors functionally linked to second messenger systems. Hence the basic components of a surveillance system arose "at the very beginning."
Elements of the aggressive systems we know best from studies of mammalian macrophages and neutrophils (e.g., lysosomal enzymes, proton pumps, enzyme complexes that produce reactive oxygen radicals, pore-forming molecules, etc.) are also present in unicellular eukaryotes. Studies of their roles in defense are few. However, some studies illustrate offensive use: Entamoeba histolytica, for example, rely on pore-forming molecules ("amaebapores," Bruhn and Leippe, 2001) and cysteine proteinases in the pathogenesis of invasive amebiasis (Que et al., 2002). The capacity to be aggressive has likely been essential for survival since the earliest days of cellular life.
Hundreds of millions of years passed between (i) the appearance of such recognition systems and the means of mounting aggressive responses and (ii) the appearance of RAG 1 and 2. During this time, particularly during the Cambrian explosion and subsequently, evolutionary diversification occurred on an unprecedented scale. The diversifying nature of these events yielded several phyletic lineages. Best known are the protostome and deuterostome lineages, the latter eventually giving rise to the vertebrates. Less widely known is the fact that within the protostomes two major lineages also evolved (Valentine et al., 1999; Fig. 1). The relevance of this dichotomy stems from the fact that a great deal of modern biology is being discovered through detailed, predominantly molecular genetic studies of a small number of model organisms, and the fact that two of these—Caenorhabditis elegans and Drosophila melanogaster—are members of the Ecdysozoa. The sister lineage (Lophotrochozoa) includes very successful and diverse taxa such as the annelid worms (12,000 described species) and the molluscs (50,000 described species) (World Resources Institute; http://www.wri.org/wri/biodiv/f01-key.html). It is reasonable to predict that immune mechanisms in lophotrochozoan species will be informative as we strive to reconstruct the evolutionary history of immune mechanisms (Loker and Bayne, 2001).
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FIG. 1. Modern concept of the evolutionary history of the Metazoa. This phylogeny (based on data from several sources) is from Valentine et al. (1999). The supporting data are mainly molecular and developmental. Notice that two clades—the Lophotrochozoa and the Ecdysozoa—are given equal standing to that of the Deuterostomes. No major animal models currently in vogue are lophotrochozoans
Immune competence of an immunologically obscure Cambrian taxon, a mollusc
On account of the facts that (i) planorbid snails are required for humans to become infected with blood flukes (the snails serve as intermediate hosts for these trematode worms), and (ii) both naturally occurring and laboratory-bred snail strains are available that are resistant to the human parasite and therefore able to block transmission (Loker, 1994), a body of knowledge has been accumulating on the immune system of the most important host snail, Biomphalaria glabrata (Bayne et al., 2001). Structurally, its immune system is comprised of leukocytes that are produced in an hematopoietic tissue within the pericardium and that circulate in the blood, and a plethora of plasma molecules. The variety of leukocytes is restricted to just 2 morphologically distinct types: small, non-granular hyalinocytes that do not spread much on glass or plastic, and larger granulocytes that are phagocytic and have been termed macrophage-like (Bayne et al., 1980; McKerrow et al., 1985). There is a suggestion of subpopulations present within the granulocyte population (Coustau and Yoshino, 1994); this may be indicative of ontogeny or it may have functional relevance.
The quantitatively predominant plasma molecule in planorbid snails is hemoglobin. Much remains to be discovered vis-à-vis additional humoral molecules. However, a tetrameric -macroglobulin antiprotease (Bender and Bayne, 1996), a family of fibrinogen- and immunoglobulin-related multidomain proteins (Leonard et al., 2001; Zhang et al., 2001) and other molecules that are toxic to trematodes (Sapp and Loker, 2000) are among these. A cecropin-like sequence has been reported (Adema et al., unpublished GenBank #AF134472) but we do not know if this and other putatively defense-related molecules are normally free in the plasma rather than contained intracellularly. As in other spheres of biology, molecular approaches are now accelerating the rate of discovery of immune-relevant plasma molecules in molluscs (Lockyer et al., 2000; Jones et al., 2001; Knight et al., 2000; Schneider and Zelck, 2001).
Clearly, molluscan leukocytes are crucial agents of self-defense and are appropriately thought of as immunocytes. They possess both the equipment and the behavioral repertoire required to mount effective defenses such as parasite encapsulation and killing. The molecular armory that they call upon is diverse and includes pattern recognition molecules (Hahn et al., 2000), lysosomes with lytic enzymes (see Bayne, 1983), an NADPH oxidase enzyme complex producing superoxide anion (Adema et al., 1994; Hahn et al., 2000), nitric oxide synthase (Nappi and Ottaviani, 2000; Gourdon et al., 2001) and antimicrobial peptides (Mitta et al., 2000). The source and nature of the putative anti-trematode molecules (Sapp and Loker, 2000) and of opsonins (Renwrantz and Richards, 1992; Bayne and Fryer, 1994) remain unclear (van der Knaap et al., 1981). The defensive cells also express a behavioral repertoire that enables them to use these mechanisms as effective agents of defense. They are capable of chemotaxis (Kumazawa et al., 1992), degranulation (Bayne, 1983), phagocytosis, and encapsulation of objects too large to engulf.
Components of the armory of a molluscan immunocyte
Pattern recognition receptors
In animals, recognition of pathogen-associated molecular patterns is often achieved by multi-valent lectins with high affinities for complex carbohydrate structures (Janeway, 1989; Medzhitov and Janeway, 2000b). Consistent with this, leukocytes of the escargot (Helix pomatia) express receptors for mannose-6-phosphate (Renwrantz and Richards, 1992). Evidence that leukocytes of B. glabrata express pattern recognition lectins was obtained first by competitive inhibition of yeast phagocytosis using laminarin, a poly-glucose (Fryer et al., 1989). Using a fluorescence in-plate assay for the respiratory burst and, as stimulants, neo-glycoproteins (ngp; bovine-serum albumin complexed with sugars), galactose-, mannose- and fucose-ngp elicited the burst, whereas glucose-, lactose-, melibiose-, n-acetyl-D-glucosamine- and n-acetyl-D-galactosamine-ngp did not (Hahn et al., 2000) (Fig. 2). These data implicate hemocyte surface receptors that, on binding their ligands, stimulate cell production of reactive oxygen species.
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FIG. 2. Respiratory bursts of Biomphalaria glabrata hemocytes in response to various neo-glycoproteins (from Hahn et al., 2000). Percent increases in hydrogen peroxide represents the increase in oxidation of 2',7'-dichlorodihydrofluorescein-diacetate by hemocytes in a microplate assay 120 minutes after the addition of a yeast cell wall derivative (Macrogard), bovine serum albumin (BSA) or BSA divalently complexed with mannose (Man), fucose (Fuc), galactose (Gal), lactose or melibiose. Cross hatched bars represent a snail strain that is resistant to the schistosome, while the open bars represent a susceptible strain
The respiratory burst
The NADPH oxidase enzyme complex is responsible for producing superoxide anion, the initial reactant in the respiratory or oxidative burst—a cascade capable of yielding additional damaging radicals that can kill microbes (Babior, 1999). This enzyme activity was first detected for molluscs in several snail species (Dikkeboom et al., 1988a), and it was suspected to play a role in the killing of schistosome blood flukes by Lymnaea stagnalis, a species that is naturally resistant to Schistosoma mansoni (Dikkeboom et al., 1988b). Subsequently it was demonstrated that B. glabrata uses the enzyme in its killing response to S. mansoni (Adema et al., 1994; Hahn et al., 2001a; Fig. 3). As the bivalves Mytilus edulis (Noel et al., 1993), M. galloprovincialis (Arumugam et al., 2000) and the oyster Crassostrea gigas (Takahashi et al., 2000) also contain this system, it is likely present generally in the Mollusca.
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FIG. 3. The ability of Biomphalaria glabrata hemocytes to kill schistosome sporocysts is compromised by the NADPH oxidase inhibitor protocatechuic acid (PCA; adapted from Hahn et al., 2001a). Killing of parasite larvae by hemocytes from parasite-resistant snails was scored in real time by the appearance of fluorescence due to the incorporation of propidium iodide in nuclei of the parasite. Sporocyst mortality was evident whenever hemocytes were present, but PCA significantly reduced the killing
The fates of reactive oxygen species generated following superoxide anion depend largely on the nature of enzymes present at or near the sites of production. In mammalian neutrophils, myeloperoxidase is a key player, converting hydrogen peroxide to hypochlorous acid. In strains of B. glabrata that differ in their ability to kill S. mansoni sporocysts, a putative myeloperoxidase appears to be differentially expressed (Schneider and Zelck, 2001), and this may be important in determining susceptibility or resistance of the snail to the parasite (Bayne et al., 2001).
Nitric oxide synthase (NOS)
In its high output form, this enzyme serves the defensive needs of animals, since nitric oxide and the product of its reaction with superoxide (peroxynitrite) will damage proteins (Reiter et al., 2000). The mRNA for NOS has been identified in snail neurons but not (yet) in leukocytes (Moroz, 2000). We obtained indirect evidence of a defensive role for NO in the leukocyte-mediated attack of B. glabrata on the human blood fluke, Schistosoma mansoni. The arginine analog L-N-arginine methyl ester (L-NAME) but not the D isomer inhibits NOS. Consistent with the involvement of this enzyme in the leukocyte-mediated attack of B. glabrata on S. mansoni, we observed a reduction of killing when leukocytes were allowed to attack S. mansoni sporocysts in vitro in the presence of L-NAME (Hahn et al., 2001b) (Fig. 4).
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FIG. 4. When hemocytes were allowed to attack S. mansoni sporocysts in vitro, L-NAME (an inhibitor of nitric oxide synthase) reduced the killing (adapted from Hahn et al., 2001b). Killing assays resembled those used for Figure 3, with the exception that the nitric oxide inhibitor L-NAME or its inactive isomer D-NAME was present. The inhibitor significantly reduced the killing
Antimicrobial peptides
The widespread occurrence of antimicrobial peptides (Ganz, 2003) and their earlier report in various nudibranch molluscs (sea slugs; Yamazaki et al., 1990) make it unsurprising though interesting that they have been reported to occur in leukocytes of the bivalve M. galloprovincialis (Mitta et al., 2000). Sequencing of ESTs from leukocytes of B. glabrata (Schneider and Zelck, 2001) has yielded evidence of a putative defensin. Furthermore, a cecropin-like peptide has been reported in this species (Adema et al., unpublished GenBank #AF134472). Functional data are yet to be reported for either.
Anti-trematode molecules
With genome sequencing projects being completed and new ones started with increasing frequency, one anticipates discovery of novel defense-related proteins throughout phylogeny. Anti-trematode molecules will likely fall in this category. Efforts to isolate from snail plasma and to characterize molecules responsible for killing trematodes (Sapp and Loker, 2000) remain to be brought to fruition.
This cornucopia of defense-related products and cells in a species representing others that have been around for 520 to 530 million years, and that are members of the Lophotrochozoa, emphasizes the power and redundancy of innate immune systems that had evolved long before the origin of the vertebrates.
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Even towards the end of the 20th century, one might have expected to read in textbooks on immunology that immunocompetence requires a lymphoid immune system that includes the genetic raw material and the recombinase enzymes for making antibodies and T cell receptors, accessory (antigen-processing and presenting) cells, co-stimulatory ligands and receptors, cytokines and a major histocompatibility system. This is what we have all been taught. I suggest, however, that a 21st century consensus might read like this: immunocompetence requires cells and molecules that recognize and neutralize potentially dangerous infectious agents, and such cells and molecules are essential components of all eukaryotic organisms.
Figure 5 conveys the notion that the adaptive (lymphoid) arm of the vertebrate immune system was, at the time of its origin, subservient to the dominant innate arm of immunity. A pre-existing, competent, diversified armory of defensive mechanisms was joined by an army of small cells (lymphocytes) endowed with the novel capacity to produce receptors capable of specifically recognizing a huge array of epitopes. Whether these cells retained the novel receptors on the cell surface or secreted them, the receptors did little more than enable the innate immune system to better aim its offensive armory against specific targets. By analogy, one might envisage a band of hooligans armed with grenades, mace and shot-guns recruiting novices with rifles—instruments to achieve better aim. The ammunition, however, had already been developed. Among others in the comprehensive armory, there were these: a complement system with at least one activation pathway and the ability to target a diversity of molecules (Sunyer et al., 1998); a similarly promiscuous -2-macroglobulin (Mutsuro et al., 2000); and phagocytic ancestors of dendritic cells already armed with Toll-like receptors communicating with gene-activating mechanisms (Escoubas et al., 1999), cytotoxic molecules, and the abilities to make toxic radicals and cytokines. Importantly, a well developed acute phase response was likely present, as it is today in insects (Hoffmann et al., 1996) and teleosts (Bayne and Gerwick, 2001). Furthermore, immunoglobulin superfamily members were expressed on cell surfaces (Rader et al., 1996) and may even have had defensive roles (Greenberg et al., 1996; Mendoza and Faye, 1999; Zhang et al., 2001). Lacking at the time were jaws, lymphoid tissues, RAG 1 and 2, and bone marrow.
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FIG. 5. Evolutionary history of innate and "adaptive" (recombinatory) arms of immunity. The "organism" represents a generic internal defense system. When recombinases (RAG) first acted on members of the immunoglobulin superfamily to give birth to adaptive immunity, the products of these events found utility as antigen recognition molecules that helped the pre-existing diverse repertoire of innate defenses achieve their ancient roles. A putative neural origin of adaptive immunity is suggested. Precise locations of words should not be interpreted to imply a precise chronology of origins; the basis for such dating is generally not available
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For most of the long history of the evolution of life on this planet, the essential components of self defense systems have existed. Both surveillance to detect dangerous chemical signatures and aggression to neutralize the bearers of those signatures arose early and were retained. The armory of aggressive "weapons" diversified and evolved to encompass practically all of the gene systems that now effect immune defenses in modern mammals. Late in evolution (ca. 430 million years ago), the horizontal transfer of a transposase from a prokaryote to a primitive vertebrate provided the means to create large numbers of distinct receptors that were recruited into the service of the defense system.
Whereas in vitro assays of lymphocyte responsiveness, widely used in the mid-twentieth century, created the impression of an autonomous adaptive immune system, it has more recently become appreciated that the armies of lymphocytes serve at the behest of phagocytic cells of the myeloid series. It remains to be determined if any aspects of lymphoid function operate autonomously in vivo.
Is the adaptive immune system an evolutionary off-shoot of the vertebrate nervous system?
As though to tickle the imagination, it appears that the acquisition of RAG genes may have coincided with the elaboration of neural crest and tissues derived from it, such as jaws, at a time of increasing complexity of the nervous system. The possible relevance of this becomes evident when we consider insights suggested first by Bill Hildemann and his associates (Hildemann et al., 1979), who drew attention to the fact that the vertebrate immune and nervous systems share the properties of specific recognition, memory and the abilities to mount and target aggressive responses. A growing number of "neuro"-transmitters are now known to be made by and are active in the immune system (Schauenstein et al., 2000), and a growing number of "cytokines" are made by and active in the nervous system (Dunn, 2000). Indeed, it has been convincingly established that neuro-immune cross-talk is essential to homeostasis throughout the vertebrates. What is most intriguing here is that at least some of the signaling molecules mediating this communication are shared by neural and immune systems. Lately, the understanding of immune processes has benefited from the concept of the immunological synapse, a cell-cell interface structurally and functionally reminiscent of the neural synapse (Krummel and Davis, 2002). Given all these considerations, perhaps it is not so revolutionary to suggest that the adaptive immune system is an evolutionary off-shoot of the vertebrate nervous system! This notion is encouraged by the recent discovery that immunoglobulin superfamily members facilitate correct targeting of neuronal axons in the developing nervous systems in animals as primitive as C. elegans (Aurelio et al., 2002). The proper wiring of complex nervous systems, of course, requires very large numbers of specific ligands and receptors. The hypothesis suggested here predicts the existence, in the developing nervous systems of all gnathostomes, of a system for generating high levels of diversity in such an address system.
ACKNOWLEDGMENTS
I thank Randall Bender and three anonymous reviewers for constructive suggestions after critically reading the draft manuscript. Both R. C. Bender and Ulrike Hahn contributed most of the experiments in the data section of this paper. We have been supported by NIH awards AI-16137, and ES-03850.
FOOTNOTES
1 From the Symposium Comparative Immunology presented at the Annual Meeting of the Society for Integrative and Comparative Biology, 2–6 January 2002, at Anaheim, California.
2 E-mail: baynec@bcc.orst.edu
3 "inappropriate" because it implies that other components of immunity are somehow not adaptive—obviously a false notion (Bayne, 1995).
References
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Online ISSN 1557-7023 - Print ISSN 1540-7063 Copyright © 2008 The Society for Integrative and Comparative Biology Oxford Journals Oxford University Press Site Map Privacy Policy Frequently Asked Questions
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Kyungmin Hahm, Eleanor Y. M. Sum, Yuko Fujiwara, Geoffrey J. Lindeman, Jane E. Visvader, and Stuart H. Orkin
Mol. Cell. Biol., Mar 2004; 24: 2074 - 2082.
LMO4 belongs to a family of transcriptional regulators that comprises two zinc-binding LIM domains.
LIM-only (LMO) proteins appear to function as docking sites for other factors, leading to the assembly of multiprotein complexes.
The transcription factor Deaf-1/NUDR has been identified as one partner protein of LMO4.
We have disrupted the Lmo4 and Deaf-1 genes in mice to define their biological function in vivo.
All Lmo4 mutants died shortly after birth and showed defects within the presphenoid bone, with 50% of mice also exhibiting exencephaly.
Homeotic transformations were observed in Lmo4-null embryos and newborn mice, but with incomplete penetrance. These included skeletal defects in cervical vertebrae and the rib cage. Furthermore, fusions of cranial nerves IX and X and defects in cranial nerve V were apparent in some Lmo4-/- and Lmo4+/- mice.
Remarkably, Deaf-1 mutants displayed phenotypic abnormalities similar to those observed in Lmo4 mutants.
These included exencephaly, transformation of cervical segments, and rib cage abnormalities. In contrast to Lmo4 nullizygous mice, nonexencephalic Deaf-1 mutants remained healthy. No defects in the sphenoid bone or cranial nerves were apparent. Thus, Lmo4 and Deaf-1 mutant mice exhibit overlapping as well as distinct phenotypes.
Our data indicate an important role for these two transcriptional regulators in pathways affecting neural tube closure and skeletal patterning, most likely reflecting their presence in a functional complex in vivo.
DEAF-1 regulates immunity gene expression in Drosophila
Darien E. Reed*, Xinhua M. Huang, James A. Wohlschlegel, Michael S. Levine,, and Kate Senger,¶
*Helen Diller Family Comprehensive Cancer Center and Cancer Research Institute, University of California, San Francisco, CA 94115-0128; Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, CA 90095-1737; Department of Molecular and Cell Biology, Division of Genetics, Genomics, and Development, Center for Integrative Genomics, University of California, Berkeley, CA 94720-3200; and ¶Department of Immunology Discovery, Genentech, South San Francisco, CA 94080-4990
Contributed by Michael S. Levine, March 31, 2008 (sent for review February 2, 2008)
Abstract
Immunity genes are activated in the Drosophila fat body by Rel and GATA transcription factors.
Here, we present evidence that an additional regulatory factor, deformed epidermal autoregulatory factor-1 (DEAF-1), also contributes to the immune response and is specifically important for the induction of two genes encoding antimicrobial peptides, Metchnikowin (Mtk) and Drosomycin (Drs).
The systematic mutagenesis of a minimal Mtk 5' enhancer identified a sequence motif essential for both a response to LPS preparations in S2 cells and activation in the larval fat body in response to bacterial infection.
Using affinity chromatography coupled to multidimensional protein identification technology (MudPIT), we identified DEAF-1 as a candidate regulator.
DEAF-1 activates the expression of Mtk and Drs promoter-luciferase fusion genes in S2cells.
SELEX assays and footprinting data indicate that DEAF-1 binds to and activates Mtk and Drs regulatory DNAs via a TTCGGBT motif.
The insertion of this motif into the Diptericin (Dpt) regulatory region confers DEAF-1 responsiveness to this normally DEAF-1-independent enhancer.
The coexpression of DEAF-1 with Dorsal, Dif, and Relish results in the synergistic activation of transcription.
We propose that DEAF-1 is a regulator of Drosophila immunity.
J Biol Chem, Vol. 273, Issue 22, 13746-13752, May 29, 1998
Overexpression of a Novel Xenopus Rel mRNA Gene Induces Tumors in Early Embryos
Saoshan Yang, Ann Lockwood, Peter Hollett, Rebecca Ford, and Kenneth Kao
From the Terry Fox Cancer Research Laboratory, Division of Basic Medical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland A1B 3V6, Canada
The Rel family of transcriptional activators form a large diverse group of proteins that are involved in the activation of genes involved in immunity, development, apoptosis and cancer. So far, none of the rel genes cloned in mammals appear to be required for embryonic development. We have cloned and characterized a cDNA from an embryonic cDNA library that encodes a novel Xenopus Rel protein, called Xrel3. Xrel3 is a member of the cRel subfamily and is most closely related to but distinct from other Xenopus Rel members. The expression of Xrel3 mRNA was investigated using Northern analysis, RNase protection assay, reverse transcriptase-linked polymerase chain reaction and in situ hybridization. Messages are present maternally and are slightly enriched in the equatorial region of the blastula stage embryo. At gastrulation, the accumulation of Xrel3 messages declines to undetectable levels but then increases after neurulation. In situ RNA hybridization was used to determine the spatial location of Xrel3 messenger RNA in embryos. Messages are localized to the developing forebrain, dorsal mid-hindbrain region, the inner ear primordium, or otocyst, and in the notochord. Overexpression by microinjection of Xrel3 RNA induced tumors in the developing embryo that appeared after gastrulation. The location of the tumors depended on the location of the injection site. These results suggest that Xrel3 might have a generalized role in regulation of cell differentiation in the embryo
Médecine/Science | Décembre 2005 | Volume 21 | n° 12
Les cellules souches embryonnaires : du développement myocardique à la médecine régénératrice
Embryonic stem cells to study early myocardial development and potential regenerative medicine
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Integrative and Comparative Biology 2003 43(2):293-299; doi:10.1093/icb/43.2.293
© 2003 by The Society for Integrative and Comparative Biology
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Origins and Evolutionary Relationships Between the Innate and Adaptive Arms of Immune Systems1
Christopher J. Bayne2,1
1 Department of Zoology, Oregon State University, Corvallis, Oregon 97331-2914
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Long before vertebrates first appeared, protists, plants and animals had evolved diverse, effective systems of innate immunity. Ancestors of the vertebrates utilized components of the complement system, protease-inhibitors, metal-binding proteins, carbohydrate-binding proteins and other plasma-born molecules as humoral agents of defense. In these same animals, immunocytes endowed with a repertoire of defensive behaviors expressed Toll-like receptors. They made NADPH oxidase, superoxide dismutase and other respiratory burst enzymes to produce toxic oxygen radicals, and nitric oxide synthase to produce nitric oxide. Antimicrobial peptides and lytic enzymes were in their armory. Immune responses were orchestrated by cytokines. Furthermore, genes within the immunoglobulin superfamily were expressed to meet a variety of needs possibly including defense. However, recombination activating genes played no role. With the acquisition of one or more transposases and the resulting capacity to generate diverse receptors from immunoglobulin gene fragments, the adaptive (lymphoid) arm of the immune system was born. This may have coincided with the elaboration of the neural crest. Naturally, the role of the adaptive arm was initially subservient to the defensive functions of the pre-existing innate arm. The strong selective advantages that stemmed from having "sharp-shooters" (cells making antigen-specific receptors) on the defense team ensured their retention. Refined through evolution, adaptive immunity, even in mammals, remains dependent upon cells of the innate series (e.g., dendritic cells) for signals driving their functional maturation. This paper calls for some fresh thinking leading to a clearer vision of the origins and co-evolution of the two arms of modern immune systems, and suggests a possible neural origin for the adaptive immune system.
INTRODUCTION
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INTRODUCTION
IMMUNE COMPETENCE
MERELY ATTITUDE ADJUSTMENT, OR...
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With few exceptions, the study of immunology has—for the past several decades at least—been predominantly the study of lymphoid biology. And what a fascinating story it has turned out to be: each individual of a species will acquire—de novo—receptors able to recognize with exquisite specificity a huge variety of foreign antigens. For each antigen that is subsequently re-encountered, lymphocytes recognizing the antigen will remember the previous encounter and respond more effectively.
In the 1970s, the influential comparative immunologist Bill Hildemann catalyzed a re-examination of the concepts of immuno-phylogeny (Hildemann et al., 1981). Hildemann appreciated that, in pioneering studies of inflammation and phagocytosis, Eli Metchnikof, the father of immunology, had made use of rose thorns, water fleas and starfish larvae. Attracted by the opportunity to "do immunology" in coral reefs, Hildemann focused the mind of a classical immunogeneticist first on experiments of Nature and later on laboratory-based "grafting" experiments with corals and sponges (Hildemann et al., 1979).
Further illustrating the prodigious fruitfulness that can result when a mind that is well informed in one area engages another, microbiologist Hans Boman in Sweden simultaneously initiated studies of the basis for acquired resistance to bacterial pathogens in insects (Boman, 1998). That work catalyzed the discovery of antimicrobial peptides throughout phylogeny, and eventually the discovery of immune functions for Toll and Toll-like receptors, and the NFB/Rel system of transcriptional activators (Medzhitov and Janeway, 2000a). Starting in the mid-20th century and continuing to the present, additional free-thinking individualists, more interested in basic biology than in joining the mainstream, have sought to discover non-immunoglobulin based mechanisms of defense. This relatively small cadre of scientists have contributed significantly to the refinement of ideas on the evolution of immunity, through efforts to understand how animals lacking lymphoid systems manage to survive in a world replete with both micro- and macro-pathogens and parasites (see as an example Beck et al., 2001).
As is now generally appreciated, the ability to recombine germline-encoded gene segments and to synthesize numerous unique antigen-recognizing receptor proteins encoded by the novel reading frames was acquired about 430 million years ago in organisms resembling primitive jawed fishes. Genes encoding members of the immunoglobulin superfamily had been expressed for hundreds of millions of years prior to that time, and their functions are thought to have been predominantly though not exclusively non-defensive (e.g., Aurelio et al., 2002). Recent thinking envisages the lateral transfer of a prokaryotic transposase with an aptitude to create recombinants out of pre-existing immunoglobulin gene segments (Agrawal, 2000). This event spawned the now inappropriate term3 "adaptive immune system."
Seduced by the impressive sophistication (or is it mere complexity?) of lymphoid biology in modern birds and mammals, some immunologists have tended to view all components of innate immunity as subservient to the adaptive arm of the immune system. An influential voice encouraging a change in perspective has been that of Charles Janeway (2001). The present paper contributes to the call for reconsideration by examining the immune landscape around the time when the transposases supposedly invaded and quickly evolved into the recombination activating genes (RAG 1 and 2) in early gnathostomes (Flajnik and Kasahara, 2001). In doing this, it crystallizes the tantalizing notion that the adaptive arm of the immune system may be an evolutionary offshoot of the nervous system.
IMMUNE COMPETENCE
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SYNOPSIS
INTRODUCTION
IMMUNE COMPETENCE
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Being immunocompetent means being able to defend oneself against potentially damaging microbes and parasites. And because neoplasia can be fatal, guarding against it has come to be seen as a second criterion of immunocompetence. This capacity to protect oneself requires both a means of surveillance (detection) and the means to neutralize the threat. Both capabilities appeared very early in the history of the evolution of life. Navigating away from life-threatening conditions and towards nutrients requires discriminating senses and appropriate behaviors that are seen even in prokaryotes. Among unicellular protists (eukaryotes), propagation depends on the ability to discriminate between different mating types, made possible by the presence of specific markers and recognition receptors functionally linked to second messenger systems. Hence the basic components of a surveillance system arose "at the very beginning."
Elements of the aggressive systems we know best from studies of mammalian macrophages and neutrophils (e.g., lysosomal enzymes, proton pumps, enzyme complexes that produce reactive oxygen radicals, pore-forming molecules, etc.) are also present in unicellular eukaryotes. Studies of their roles in defense are few. However, some studies illustrate offensive use: Entamoeba histolytica, for example, rely on pore-forming molecules ("amaebapores," Bruhn and Leippe, 2001) and cysteine proteinases in the pathogenesis of invasive amebiasis (Que et al., 2002). The capacity to be aggressive has likely been essential for survival since the earliest days of cellular life.
Hundreds of millions of years passed between (i) the appearance of such recognition systems and the means of mounting aggressive responses and (ii) the appearance of RAG 1 and 2. During this time, particularly during the Cambrian explosion and subsequently, evolutionary diversification occurred on an unprecedented scale. The diversifying nature of these events yielded several phyletic lineages. Best known are the protostome and deuterostome lineages, the latter eventually giving rise to the vertebrates. Less widely known is the fact that within the protostomes two major lineages also evolved (Valentine et al., 1999; Fig. 1). The relevance of this dichotomy stems from the fact that a great deal of modern biology is being discovered through detailed, predominantly molecular genetic studies of a small number of model organisms, and the fact that two of these—Caenorhabditis elegans and Drosophila melanogaster—are members of the Ecdysozoa. The sister lineage (Lophotrochozoa) includes very successful and diverse taxa such as the annelid worms (12,000 described species) and the molluscs (50,000 described species) (World Resources Institute; http://www.wri.org/wri/biodiv/f01-key.html). It is reasonable to predict that immune mechanisms in lophotrochozoan species will be informative as we strive to reconstruct the evolutionary history of immune mechanisms (Loker and Bayne, 2001).
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FIG. 1. Modern concept of the evolutionary history of the Metazoa. This phylogeny (based on data from several sources) is from Valentine et al. (1999). The supporting data are mainly molecular and developmental. Notice that two clades—the Lophotrochozoa and the Ecdysozoa—are given equal standing to that of the Deuterostomes. No major animal models currently in vogue are lophotrochozoans
Immune competence of an immunologically obscure Cambrian taxon, a mollusc
On account of the facts that (i) planorbid snails are required for humans to become infected with blood flukes (the snails serve as intermediate hosts for these trematode worms), and (ii) both naturally occurring and laboratory-bred snail strains are available that are resistant to the human parasite and therefore able to block transmission (Loker, 1994), a body of knowledge has been accumulating on the immune system of the most important host snail, Biomphalaria glabrata (Bayne et al., 2001). Structurally, its immune system is comprised of leukocytes that are produced in an hematopoietic tissue within the pericardium and that circulate in the blood, and a plethora of plasma molecules. The variety of leukocytes is restricted to just 2 morphologically distinct types: small, non-granular hyalinocytes that do not spread much on glass or plastic, and larger granulocytes that are phagocytic and have been termed macrophage-like (Bayne et al., 1980; McKerrow et al., 1985). There is a suggestion of subpopulations present within the granulocyte population (Coustau and Yoshino, 1994); this may be indicative of ontogeny or it may have functional relevance.
The quantitatively predominant plasma molecule in planorbid snails is hemoglobin. Much remains to be discovered vis-à-vis additional humoral molecules. However, a tetrameric -macroglobulin antiprotease (Bender and Bayne, 1996), a family of fibrinogen- and immunoglobulin-related multidomain proteins (Leonard et al., 2001; Zhang et al., 2001) and other molecules that are toxic to trematodes (Sapp and Loker, 2000) are among these. A cecropin-like sequence has been reported (Adema et al., unpublished GenBank #AF134472) but we do not know if this and other putatively defense-related molecules are normally free in the plasma rather than contained intracellularly. As in other spheres of biology, molecular approaches are now accelerating the rate of discovery of immune-relevant plasma molecules in molluscs (Lockyer et al., 2000; Jones et al., 2001; Knight et al., 2000; Schneider and Zelck, 2001).
Clearly, molluscan leukocytes are crucial agents of self-defense and are appropriately thought of as immunocytes. They possess both the equipment and the behavioral repertoire required to mount effective defenses such as parasite encapsulation and killing. The molecular armory that they call upon is diverse and includes pattern recognition molecules (Hahn et al., 2000), lysosomes with lytic enzymes (see Bayne, 1983), an NADPH oxidase enzyme complex producing superoxide anion (Adema et al., 1994; Hahn et al., 2000), nitric oxide synthase (Nappi and Ottaviani, 2000; Gourdon et al., 2001) and antimicrobial peptides (Mitta et al., 2000). The source and nature of the putative anti-trematode molecules (Sapp and Loker, 2000) and of opsonins (Renwrantz and Richards, 1992; Bayne and Fryer, 1994) remain unclear (van der Knaap et al., 1981). The defensive cells also express a behavioral repertoire that enables them to use these mechanisms as effective agents of defense. They are capable of chemotaxis (Kumazawa et al., 1992), degranulation (Bayne, 1983), phagocytosis, and encapsulation of objects too large to engulf.
Components of the armory of a molluscan immunocyte
Pattern recognition receptors
In animals, recognition of pathogen-associated molecular patterns is often achieved by multi-valent lectins with high affinities for complex carbohydrate structures (Janeway, 1989; Medzhitov and Janeway, 2000b). Consistent with this, leukocytes of the escargot (Helix pomatia) express receptors for mannose-6-phosphate (Renwrantz and Richards, 1992). Evidence that leukocytes of B. glabrata express pattern recognition lectins was obtained first by competitive inhibition of yeast phagocytosis using laminarin, a poly-glucose (Fryer et al., 1989). Using a fluorescence in-plate assay for the respiratory burst and, as stimulants, neo-glycoproteins (ngp; bovine-serum albumin complexed with sugars), galactose-, mannose- and fucose-ngp elicited the burst, whereas glucose-, lactose-, melibiose-, n-acetyl-D-glucosamine- and n-acetyl-D-galactosamine-ngp did not (Hahn et al., 2000) (Fig. 2). These data implicate hemocyte surface receptors that, on binding their ligands, stimulate cell production of reactive oxygen species.
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FIG. 2. Respiratory bursts of Biomphalaria glabrata hemocytes in response to various neo-glycoproteins (from Hahn et al., 2000). Percent increases in hydrogen peroxide represents the increase in oxidation of 2',7'-dichlorodihydrofluorescein-diacetate by hemocytes in a microplate assay 120 minutes after the addition of a yeast cell wall derivative (Macrogard), bovine serum albumin (BSA) or BSA divalently complexed with mannose (Man), fucose (Fuc), galactose (Gal), lactose or melibiose. Cross hatched bars represent a snail strain that is resistant to the schistosome, while the open bars represent a susceptible strain
The respiratory burst
The NADPH oxidase enzyme complex is responsible for producing superoxide anion, the initial reactant in the respiratory or oxidative burst—a cascade capable of yielding additional damaging radicals that can kill microbes (Babior, 1999). This enzyme activity was first detected for molluscs in several snail species (Dikkeboom et al., 1988a), and it was suspected to play a role in the killing of schistosome blood flukes by Lymnaea stagnalis, a species that is naturally resistant to Schistosoma mansoni (Dikkeboom et al., 1988b). Subsequently it was demonstrated that B. glabrata uses the enzyme in its killing response to S. mansoni (Adema et al., 1994; Hahn et al., 2001a; Fig. 3). As the bivalves Mytilus edulis (Noel et al., 1993), M. galloprovincialis (Arumugam et al., 2000) and the oyster Crassostrea gigas (Takahashi et al., 2000) also contain this system, it is likely present generally in the Mollusca.
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FIG. 3. The ability of Biomphalaria glabrata hemocytes to kill schistosome sporocysts is compromised by the NADPH oxidase inhibitor protocatechuic acid (PCA; adapted from Hahn et al., 2001a). Killing of parasite larvae by hemocytes from parasite-resistant snails was scored in real time by the appearance of fluorescence due to the incorporation of propidium iodide in nuclei of the parasite. Sporocyst mortality was evident whenever hemocytes were present, but PCA significantly reduced the killing
The fates of reactive oxygen species generated following superoxide anion depend largely on the nature of enzymes present at or near the sites of production. In mammalian neutrophils, myeloperoxidase is a key player, converting hydrogen peroxide to hypochlorous acid. In strains of B. glabrata that differ in their ability to kill S. mansoni sporocysts, a putative myeloperoxidase appears to be differentially expressed (Schneider and Zelck, 2001), and this may be important in determining susceptibility or resistance of the snail to the parasite (Bayne et al., 2001).
Nitric oxide synthase (NOS)
In its high output form, this enzyme serves the defensive needs of animals, since nitric oxide and the product of its reaction with superoxide (peroxynitrite) will damage proteins (Reiter et al., 2000). The mRNA for NOS has been identified in snail neurons but not (yet) in leukocytes (Moroz, 2000). We obtained indirect evidence of a defensive role for NO in the leukocyte-mediated attack of B. glabrata on the human blood fluke, Schistosoma mansoni. The arginine analog L-N-arginine methyl ester (L-NAME) but not the D isomer inhibits NOS. Consistent with the involvement of this enzyme in the leukocyte-mediated attack of B. glabrata on S. mansoni, we observed a reduction of killing when leukocytes were allowed to attack S. mansoni sporocysts in vitro in the presence of L-NAME (Hahn et al., 2001b) (Fig. 4).
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FIG. 4. When hemocytes were allowed to attack S. mansoni sporocysts in vitro, L-NAME (an inhibitor of nitric oxide synthase) reduced the killing (adapted from Hahn et al., 2001b). Killing assays resembled those used for Figure 3, with the exception that the nitric oxide inhibitor L-NAME or its inactive isomer D-NAME was present. The inhibitor significantly reduced the killing
Antimicrobial peptides
The widespread occurrence of antimicrobial peptides (Ganz, 2003) and their earlier report in various nudibranch molluscs (sea slugs; Yamazaki et al., 1990) make it unsurprising though interesting that they have been reported to occur in leukocytes of the bivalve M. galloprovincialis (Mitta et al., 2000). Sequencing of ESTs from leukocytes of B. glabrata (Schneider and Zelck, 2001) has yielded evidence of a putative defensin. Furthermore, a cecropin-like peptide has been reported in this species (Adema et al., unpublished GenBank #AF134472). Functional data are yet to be reported for either.
Anti-trematode molecules
With genome sequencing projects being completed and new ones started with increasing frequency, one anticipates discovery of novel defense-related proteins throughout phylogeny. Anti-trematode molecules will likely fall in this category. Efforts to isolate from snail plasma and to characterize molecules responsible for killing trematodes (Sapp and Loker, 2000) remain to be brought to fruition.
This cornucopia of defense-related products and cells in a species representing others that have been around for 520 to 530 million years, and that are members of the Lophotrochozoa, emphasizes the power and redundancy of innate immune systems that had evolved long before the origin of the vertebrates.
MERELY ATTITUDE ADJUSTMENT, OR A PARADIGM SHIFT?
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Even towards the end of the 20th century, one might have expected to read in textbooks on immunology that immunocompetence requires a lymphoid immune system that includes the genetic raw material and the recombinase enzymes for making antibodies and T cell receptors, accessory (antigen-processing and presenting) cells, co-stimulatory ligands and receptors, cytokines and a major histocompatibility system. This is what we have all been taught. I suggest, however, that a 21st century consensus might read like this: immunocompetence requires cells and molecules that recognize and neutralize potentially dangerous infectious agents, and such cells and molecules are essential components of all eukaryotic organisms.
Figure 5 conveys the notion that the adaptive (lymphoid) arm of the vertebrate immune system was, at the time of its origin, subservient to the dominant innate arm of immunity. A pre-existing, competent, diversified armory of defensive mechanisms was joined by an army of small cells (lymphocytes) endowed with the novel capacity to produce receptors capable of specifically recognizing a huge array of epitopes. Whether these cells retained the novel receptors on the cell surface or secreted them, the receptors did little more than enable the innate immune system to better aim its offensive armory against specific targets. By analogy, one might envisage a band of hooligans armed with grenades, mace and shot-guns recruiting novices with rifles—instruments to achieve better aim. The ammunition, however, had already been developed. Among others in the comprehensive armory, there were these: a complement system with at least one activation pathway and the ability to target a diversity of molecules (Sunyer et al., 1998); a similarly promiscuous -2-macroglobulin (Mutsuro et al., 2000); and phagocytic ancestors of dendritic cells already armed with Toll-like receptors communicating with gene-activating mechanisms (Escoubas et al., 1999), cytotoxic molecules, and the abilities to make toxic radicals and cytokines. Importantly, a well developed acute phase response was likely present, as it is today in insects (Hoffmann et al., 1996) and teleosts (Bayne and Gerwick, 2001). Furthermore, immunoglobulin superfamily members were expressed on cell surfaces (Rader et al., 1996) and may even have had defensive roles (Greenberg et al., 1996; Mendoza and Faye, 1999; Zhang et al., 2001). Lacking at the time were jaws, lymphoid tissues, RAG 1 and 2, and bone marrow.
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FIG. 5. Evolutionary history of innate and "adaptive" (recombinatory) arms of immunity. The "organism" represents a generic internal defense system. When recombinases (RAG) first acted on members of the immunoglobulin superfamily to give birth to adaptive immunity, the products of these events found utility as antigen recognition molecules that helped the pre-existing diverse repertoire of innate defenses achieve their ancient roles. A putative neural origin of adaptive immunity is suggested. Precise locations of words should not be interpreted to imply a precise chronology of origins; the basis for such dating is generally not available
FURTHER SPECULATIONS
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SYNOPSIS
INTRODUCTION
IMMUNE COMPETENCE
MERELY ATTITUDE ADJUSTMENT, OR...
FURTHER SPECULATIONS
References
For most of the long history of the evolution of life on this planet, the essential components of self defense systems have existed. Both surveillance to detect dangerous chemical signatures and aggression to neutralize the bearers of those signatures arose early and were retained. The armory of aggressive "weapons" diversified and evolved to encompass practically all of the gene systems that now effect immune defenses in modern mammals. Late in evolution (ca. 430 million years ago), the horizontal transfer of a transposase from a prokaryote to a primitive vertebrate provided the means to create large numbers of distinct receptors that were recruited into the service of the defense system.
Whereas in vitro assays of lymphocyte responsiveness, widely used in the mid-twentieth century, created the impression of an autonomous adaptive immune system, it has more recently become appreciated that the armies of lymphocytes serve at the behest of phagocytic cells of the myeloid series. It remains to be determined if any aspects of lymphoid function operate autonomously in vivo.
Is the adaptive immune system an evolutionary off-shoot of the vertebrate nervous system?
As though to tickle the imagination, it appears that the acquisition of RAG genes may have coincided with the elaboration of neural crest and tissues derived from it, such as jaws, at a time of increasing complexity of the nervous system. The possible relevance of this becomes evident when we consider insights suggested first by Bill Hildemann and his associates (Hildemann et al., 1979), who drew attention to the fact that the vertebrate immune and nervous systems share the properties of specific recognition, memory and the abilities to mount and target aggressive responses. A growing number of "neuro"-transmitters are now known to be made by and are active in the immune system (Schauenstein et al., 2000), and a growing number of "cytokines" are made by and active in the nervous system (Dunn, 2000). Indeed, it has been convincingly established that neuro-immune cross-talk is essential to homeostasis throughout the vertebrates. What is most intriguing here is that at least some of the signaling molecules mediating this communication are shared by neural and immune systems. Lately, the understanding of immune processes has benefited from the concept of the immunological synapse, a cell-cell interface structurally and functionally reminiscent of the neural synapse (Krummel and Davis, 2002). Given all these considerations, perhaps it is not so revolutionary to suggest that the adaptive immune system is an evolutionary off-shoot of the vertebrate nervous system! This notion is encouraged by the recent discovery that immunoglobulin superfamily members facilitate correct targeting of neuronal axons in the developing nervous systems in animals as primitive as C. elegans (Aurelio et al., 2002). The proper wiring of complex nervous systems, of course, requires very large numbers of specific ligands and receptors. The hypothesis suggested here predicts the existence, in the developing nervous systems of all gnathostomes, of a system for generating high levels of diversity in such an address system.
ACKNOWLEDGMENTS
I thank Randall Bender and three anonymous reviewers for constructive suggestions after critically reading the draft manuscript. Both R. C. Bender and Ulrike Hahn contributed most of the experiments in the data section of this paper. We have been supported by NIH awards AI-16137, and ES-03850.
FOOTNOTES
1 From the Symposium Comparative Immunology presented at the Annual Meeting of the Society for Integrative and Comparative Biology, 2–6 January 2002, at Anaheim, California.
2 E-mail: baynec@bcc.orst.edu
3 "inappropriate" because it implies that other components of immunity are somehow not adaptive—obviously a false notion (Bayne, 1995).
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