cAMP System Research Articles

CAMP signalling in insulin and glucagon secretion.

The "second messenger" archetype cAMP is one of the most important cellular signalling molecules with central functions including the regulation of insulin and glucagon secretion from the pancreatic β- and α-cells, respectively. cAMP is generally considered as an amplifier of insulin secretion triggered by Ca2+ elevation in the β-cells. Both messengers are also positive modulators of glucagon release from α-cells, but in this case cAMP may be the important regulator and Ca2+ have a more permissive role. The actions of cAMP are mediated by protein kinase A (PKA) and the guanine nucleotide exchange factor Epac. The present review focuses on how cAMP is regulated by nutrients, hormones and neural factors in β- and α-cells via adenylyl cyclase-catalysed generation and phosphodiesterase-mediated degradation. We will also discuss how PKA and Epac affect ion fluxes and the secretory machinery to transduce the stimulatory effects on insulin and glucagon secretion. Finally, we will briefly describe disturbances of the cAMP system associated with diabetes and how cAMP signalling can be targeted to normalize hypo- and hypersecretion of insulin and glucagon, respectively, in diabetic patients.

David-Fox, Michael (ed.) The Soviet Gulag: Evidence, Interpretation, and Comparison (review)

REVIEWS 581 David-Fox, Michael (ed.). The Soviet Gulag: Evidence, Interpretation, and Comparison. Pitt Series in Russian and East European Studies; Kritika Historical Studies. University of Pittsburgh Press, Pittsburgh, PA, 2016. xi + 434 pp. Map. Illustrations. Tables. Notes. Index. $49.95. Expanding on the articles presented in a special issue of the journal, Kritika: Explorations in Russian and Eurasian History (2015), this new collection of essays brings together some of the most important new scholarship on the Gulag. Focusing broadly on questions such as the productivity of the Gulag, its significance as a representation of modernity and the applicability — or otherwise — of Giorgio Agamben’s conception of the ‘state of exception’ to the Sovietcamps,theessaysmarktheshiftinemphasisofrecentresearchawayfrom Aleksandr Solzhenitsyn’s ‘archipelago’ model. The nebulous borders between Gulag and ‘non-Gulag’, as defined in Oleg Khlevniuk’s contribution, provide a fruitful framework for the analyses by several authors. Golfo Alexopoulos and Dan Healey explore different sides of the question of debilitated and disabled convicts. Alexopoulos, taking Solzhenitsyn’s coinage, ‘destructive labour camps’, as her starting point, documents the catastrophic effect of hard labour on convicts’ health and the use of early release to maintain camp mortality figures at an artificially low level, to argue that the Gulag was ‘more lethal than corrective’ (p. 42). Healey, conversely, examines moves to both accommodate and exploit the labour of disabled prisoners as a factor that fundamentally undermined the economic viability of the Gulag. Equally revealing of the contradictory imperatives governing the Gulag, and likewise taking disabled prisoners as a major focus, is Wilson T. Bell’s local study of the Western Siberian Gulag during the Second World War. Asif Siddiqi’s exploration of Stalinist sharashkas shows how these specialist institutes became a source of agency for scientists, who could regain a degree of control over their lives by agreeing to work on the state’s projects. Renamed and placed under new leadership after the death of Stalin, many of these operations exist to this day, one way in which the contours of the Gulag remain visible and continue to impact on Russian society and institutions. Alloftheabove-mentionedessaysrelyforevidencetoagreaterorlesserextent on Gulag memoirs, both published and unpublished. As an abundant and stillgrowing source, written testimonies by survivors have always been a mainstay of Gulag research and cannot be ignored. However, none of the essays discuss the methodological questions raised by using such sources, an omission that is underlined by the last two articles in the first section. Emilia Koustova’s examination of integration in special settlements gives a clear account of her analysis of oral testimonies and their construction as narratives, while Aglaya K. Glebova’s thought-provoking ‘Nine Theses’ explicitly shapes a methodology for a visual history of the Gulag. A similar consideration of the use of memoir SEER, 95, 3, JULY 2017 582 material and the problematics of deploying narrative as historical evidence, either as a separate essay or within one or more of the other contributions, would have been a welcome addition to the collection. As part of the current trend towards transnational histories, the second, comparative section of the book addresses concentration camps and mass detention in the British Empire, Nazi forced labour camps and the Chinese and North Korean camp systems. The latter two articles, by Klaus Mülhahn and Sungmin Cho respectively, represent emerging fields of research, facing similar obstacles regarding access to sources and verification that confronted students of the Gulag half a century ago. On this basis alone the inclusion of these topics is welcome. Yet although this section may be the most innovative feature of the collection, the comparative elements in these essays are on the whole quite weak and generalized, with a few unfortunate inaccuracies and an over-reliance on popular histories — notably Ann Applebaum’s Gulag: A History of the Soviet Camps (London, 2004) — rather than more recent, specialist works, not least by several of the authors represented in the previous section. As a result, these essays, while interesting and informative in their own right, do not shed the sort of further light on the Gulag that one might hope for. Even Dietrich Beyrau’s careful negotiation of the potential minefield of comparing the Soviet Union and Nazi...

The ‘Piano Nomadi’ and its pyramidal governance: The hidden mechanism underlying the ‘camps system’ in Rome

This article deals with the social exclusion of Romanies/ ‘Gypsies’ in Italy and the recent implementation of a state of emergency, the so-called Emergenza Nomadi (Nomad Emergency). It provides an investigation of the interactions between local institutions, civil society organisations and Romani people inside the so called campi nomadi (nomad camps) in Rome. The major contribution of this study is that it reveals the existence of a deeply rooted mechanism of marginalisation – the ‘camps system’ – in which corruption, lack of transparency and accountability, inefficiencies and antagonisms between a variety of competing actors have contributed to reify and crystallise the Romani condition.

Violence as a human condition: Recent contributions from the German social sciences

Raume der Gewalt by Jorg Barberowski; S Fischer Verlag, Frankfurt, 2013, 272 pages, 19.99 [euro], cloth ISBN 978-3-10-004818-9 Topologie der Gewalt by Byung-Chul Han; Verlag Matthes und Seitz, Berlin, 2011, 192 pages, 19.90 [euro], cloth 978-3-88221-495-6 Vertrauen und Gewalt. Versuch uber eine besondere Konstellation der Moderne by Jan Philip Reemtsma; Hamburger Edition, Hamburg, 2013 [2008], 576 pages, 20.00 euro], cloth ISBN 978-3-86854-270-7 'Cats scratch, dogs bite, men kill' (Ruth Kluger) The phenomenon of violence still presents a unique challenge to social theory. Recent discourses on terrorism open new fields for conceptualising the phenomenon. However, it is still the experiences of the 20th century which continue to shape theoretical reflections on violence: the two world wars, the totalitarian political systems of Stalinism and National Socialist Germany, the German concentration camps and Soviet Gulag, Hiroshima and Nagasaki--the list is by far not exhaustive. Ruth Kluger, a survivor of the German concentration camp system, offers a short and lapidary account of these excesses of violence. In a conversation with Jan Reemtsma, she stated that, 'Cats scratch, dogs bite, men kill' (Reemtsma, 2013[2008], p. 15). Her statement expresses both the factuality and the incommensurability of violence in human experience. Violence is beyond explanation, and perhaps there is nothing to explain in the first place. In Kluger's statement, violence becomes a human condition. The three books under review here address the idea of violence as a human condition. All of them start from the observation that violence has far from disappeared from human experience. Yet this observation poses a problem. It is not easily reconciled with the foundational norm of modernity that violence should no longer be a part of social life. Each in its own way, the three books try to make sense of this observation and the problems which it poses for social theory. Broadly speaking, the authors reflect on three main questions: first, why does violence persist in spite of the central promise of modernity that it should disappear from our societies? Second, how do social theory and everyday practice interpret and deal with this incongruity between expectation and experience? Third, what are the specific forms of violence in (late) modernity and the more generic insights they offer about the phenomenon? The authors tackle these three questions to various degrees, from different individual and conceptual vantage points. In this review essay, I discuss their insights, reflect on the challenges violence poses to social theory, and, at the same time, outline some generic reflections on violence based on these books. All of the three books which I discuss were originally published in German, and only Reemtsma's has so far been translated to English. The three books draw to a considerable degree on sources in German language, some of which have not been translated to English either. For this reason, all of the translations of direct quotes from German to English are my own. The history of the 20th century certainly points towards a specific German experience of violence. Indeed, this history is important for the analyses of the books by Barberowski and Reemtsma. For the former, it also figures as an explicit autobiographical reference to family history. However, my aim with this review is not to suggest that there is a specific 'German' approach to theorizing violence. Rather, I seek to render accessible these authors' reflections to an English language readership. The German social sciences have a long and rich tradition of social theory on violence. Jorg Barberowski's Raume der Gewalt (Spaces of violence) explores violence as a spatial concept. A historian and philosopher whose research focuses on Eastern Europe and the Soviet Union, particularly for the Stalin era, much of his empirical material relates to German and Soviet history. …

Nikolaus Wachsmann. KL: A History of the Nazi Concentration Camps.

June 28, 2016 Harold Marcuse, Featured Review for American Historical Review, of: KL: A History of the Nazi Concentration Camps, by Nikolaus Wachsmann, (Farrar, Straus and Giroux, 2015), 865 pp., cloth $40. review: 2574 words with 130 struck through = 2444 (2500 max) The title of this prodigious but eminently readable work, KL, is programmatic. Instead of the more commonly known and used abbreviation for the German Konzentrationslager, KZ, Nikolaus Wachsmann has chosen the official Nazi abbreviation, which was guarded like a trademark by the system's potentate, Heinrich Himmler, who did not want competing camps outside of his system. KL reflects Wachsmann's attempt to roll back the veils of historiography and memory to reveal the system as seen by its contemporaries as it unfolded over time. This undertaking synthesizes numerous works of German scholarship, which since the 1990s have drawn upon a wealth of newly available sources to shed light on many aspects of the Nazi camp system. While a meticulous and innovative overview of the Nazi concentration camp system based on the latest scholarly research would already be a significant achievement, Wachsmann combines this scholarship with an encyclopedic knowledge of published and unpublished survivor accounts. The many corrective and illustrative anecdotes that lace this dense account also keep it engaging. Additionally, Wachsmann is attentive to the broader social, political and economic contexts within which the camp system evolved and operated. This enables him to revise longstanding preconceptions about the camp system, which have persisted because of its unique historiography. A look back at previous attempts to portray the entire system highlights the achievement embodied by KL. The first such attempt was made by Eugen Kogon, a non-party-affiliated anti-Nazi who was liberated from Buchenwald, where he had been imprisoned since 1939. Immediately after liberation the US Army commissioned the scholar-journalist to write a report about the camp system. Over the following months Kogon augmented and reworked his original Buchenwald Report, publishing it under the title Der SS-Staat in 1946. It was translated into English in 1950 as The Theory and Practice of Hell: The German Concentration Camps and the System Behind Them. Still in print today, the nearly 50 German editions and dozen translations of this book remained the only attempt at a comprehensive portrayal of Himmler's KL system until the 1990s. This is not to say that no scholars had written about the camps until then. Historians at the Munich Institute for Contemporary History (IfZ) compiled historical reports for the Frankfurt Auschwitz Trial in 1963, soon published under the title Anatomy of the SS-State (1965, English 1968). Typical of works during this period, they were based almost exclusively on perpetrator-

What to Read Now: When Civilization Fails

Notebook With two world wars, revolutions, famines , colonial violence, and state-sponsored genocides, the twentieth century was the most murderous in history, claiming the lives of some two hundred million people—catastrophe on a global scale, in which collapsing power structures left people exposed to unmitigated violence. Each of the three books below explores a different way a civilization can fail, reminding us how thin is the thread by which humanity hangs over the abyss, and how it is only by confronting our own nature that we can try to prevent the past from happening again. Anna Bikont The Crime and the Silence: Confronting the Massacre of Jews in Wartime Jedwabne Trans. Alissa Valles Farrar, Straus & Giroux “There’s something in man,” says one of the Holocaust survivors in Anna Bikont’s book, “that makes him like killing.” Part memoir, part investigative journalism, The Crime and the Silence is an informed and gut-wrenching reconstruction of July 10, 1941, when the Jewish residents of a small Polish town were burned alive by their Polish neighbors, a crime they subsequently blamed on the Germans. Having only recently discovered she was Jewish, Polish writer and scholar Anna Bikont makes it her personal quest to get to the definitive answer as to what exactly happened in Jedwabne, an issue that has polarized Polish society. The findings of her harrowing journey through eyewitness accounts and other surviving evidence dispel a few myths that are at the heart of Polish and European identities (her readings have been picketed by Polish nationalists) and show the endpoint to which decades of stoking fear and hatred against “the other” can take a society. Varlam Shalamov Kolyma Tales Trans. John Glad Penguin Classics Varlam Shalamov’s firsthand account of life in Stalin’s Gulag, a system of forced labor camps in northeastern Siberia, reads like a nightmare version of Jack London’s Klondike stories, where the harshness of nature is no match for the cruelty of men. In the frigid world of Kolyma, one chops off his fingers to get out of a gold shaft; a darned woolen sweater is reason to kill; and grown men cry at the sight of bread. Some are dying for days, like the Poet from “Sherry-Brandy.” Some fall flat on the ice and expire while still clinging to their mining hacks. The hopes of the living extend no further than a few hours. No crime can shock a Kolyma inmate; like bodies, souls freeze over, too. Those who retain their humanity change nothing. Unpublished during Shalamov’s life, Kolyma Tales is a monument to the millions of men and women who perished in Stalin’s camps. Saul Below considered it a book “that captures the essence of being.” Jose Eduardo Agualusa A General Theory of Oblivion Trans. Daniel Hahn Archipelago Following Angola’s path from colonialism to independence, with violent detours into war, communism, and capitalism, the Portuguese-Angolan writer Jose Eduardo Agualusa paints disaster through the eyes of an exiled Portuguese woman, Ludo, who barricades herself inside her apartment in Luanda and subsists, for twenty-eight years, on pigeons and vegetables, burning her favorite books to stay warm and writing her observations on the walls. In Oblivion, events are measured against the currency of Ludo’s universe, with revolutions and civil war appearing less important than the death of her pet, which equals the elimination of half the known world. Animals share equal space with humans on the pages of Agualusa’s book for a simple reason: “Humanity hasn’t worked out well.” Narrated in a voice reminiscent of Latin American and European classics, filled with rich imagery and existential insights, the novel borders on a dream, whose strange beauty lingers for a while after turning the last page. Russian American writer Anastasia Edel has written a novel, Past Perfect, a collection of literary essays, a short-story collection, and a nonfiction book, Russia: Putin’s Playground. She holds an MFA from Pacific University and lives in the Bay Area with her family. what to read now When Civilization Fails by Anastasia Edel 6 WLT JANUARY–FEBRUARY 2017 ...

What to Read Now: When Civilization Fails

Notebook With two world wars, revolutions, famines , colonial violence, and state-sponsored genocides, the twentieth century was the most murderous in history, claiming the lives of some two hundred million people—catastrophe on a global scale, in which collapsing power structures left people exposed to unmitigated violence. Each of the three books below explores a different way a civilization can fail, reminding us how thin is the thread by which humanity hangs over the abyss, and how it is only by confronting our own nature that we can try to prevent the past from happening again. Anna Bikont The Crime and the Silence: Confronting the Massacre of Jews in Wartime Jedwabne Trans. Alissa Valles Farrar, Straus & Giroux “There’s something in man,” says one of the Holocaust survivors in Anna Bikont’s book, “that makes him like killing.” Part memoir, part investigative journalism, The Crime and the Silence is an informed and gut-wrenching reconstruction of July 10, 1941, when the Jewish residents of a small Polish town were burned alive by their Polish neighbors, a crime they subsequently blamed on the Germans. Having only recently discovered she was Jewish, Polish writer and scholar Anna Bikont makes it her personal quest to get to the definitive answer as to what exactly happened in Jedwabne, an issue that has polarized Polish society. The findings of her harrowing journey through eyewitness accounts and other surviving evidence dispel a few myths that are at the heart of Polish and European identities (her readings have been picketed by Polish nationalists) and show the endpoint to which decades of stoking fear and hatred against “the other” can take a society. Varlam Shalamov Kolyma Tales Trans. John Glad Penguin Classics Varlam Shalamov’s firsthand account of life in Stalin’s Gulag, a system of forced labor camps in northeastern Siberia, reads like a nightmare version of Jack London’s Klondike stories, where the harshness of nature is no match for the cruelty of men. In the frigid world of Kolyma, one chops off his fingers to get out of a gold shaft; a darned woolen sweater is reason to kill; and grown men cry at the sight of bread. Some are dying for days, like the Poet from “Sherry-Brandy.” Some fall flat on the ice and expire while still clinging to their mining hacks. The hopes of the living extend no further than a few hours. No crime can shock a Kolyma inmate; like bodies, souls freeze over, too. Those who retain their humanity change nothing. Unpublished during Shalamov’s life, Kolyma Tales is a monument to the millions of men and women who perished in Stalin’s camps. Saul Below considered it a book “that captures the essence of being.” Jose Eduardo Agualusa A General Theory of Oblivion Trans. Daniel Hahn Archipelago Following Angola’s path from colonialism to independence, with violent detours into war, communism, and capitalism, the Portuguese-Angolan writer Jose Eduardo Agualusa paints disaster through the eyes of an exiled Portuguese woman, Ludo, who barricades herself inside her apartment in Luanda and subsists, for twenty-eight years, on pigeons and vegetables, burning her favorite books to stay warm and writing her observations on the walls. In Oblivion, events are measured against the currency of Ludo’s universe, with revolutions and civil war appearing less important than the death of her pet, which equals the elimination of half the known world. Animals share equal space with humans on the pages of Agualusa’s book for a simple reason: “Humanity hasn’t worked out well.” Narrated in a voice reminiscent of Latin American and European classics, filled with rich imagery and existential insights, the novel borders on a dream, whose strange beauty lingers for a while after turning the last page. Russian American writer Anastasia Edel has written a novel, Past Perfect, a collection of literary essays, a short-story collection, and a nonfiction book, Russia: Putin’s Playground. She holds an MFA from Pacific University and lives in the Bay Area with her family. what to read now When Civilization Fails by Anastasia Edel 6 WLT JANUARY–FEBRUARY 2017 ...

Beyond Intracellular Signaling: The Ins and Outs of Second Messengers Microdomains.

A typical characteristic of eukaryotic cells compared to prokaryotes is represented by the spatial heterogeneity of the different structural and functional components: for example, most of the genetic material is surrounded by a highly specific membrane structure (the nuclear membrane), continuous with, yet largely different from, the endoplasmic reticulum (ER); oxidative phosphorylation is carried out by organelles enclosed by a double membrane, the mitochondria; in addition, distinct domains, enriched in specific proteins, are present in the plasma membrane (PM) of most cells. Less obvious, but now generally accepted, is the notion that even the concentration of small molecules such as second messengers (Ca2+ and cAMP in particular) can be highly heterogeneous within cells. In the case of most organelles, the differences in the luminal levels of second messengers depend either on the existence on their membrane of proteins that allow the accumulation/release of the second messenger (e.g., in the case of Ca2+, pumps, exchangers or channels), or on the synthesis and degradation of the specific molecule within the lumen (the autonomous intramitochondrial cAMP system). It needs stressing that the existence of a surrounding membrane does not necessarily imply the existence of a gradient between the cytosol and the organelle lumen. For example, the nuclear membrane is highly permeable to both Ca2+ and cAMP (nuclear pores are permeable to solutes up to 50kDa) and differences in [Ca2+] or [cAMP] between cytoplasm and nucleoplasm are not seen in steady state and only very transiently during cell activation. A similar situation has been observed, as far as Ca2+ is concerned, in peroxisomes.

Bride and Groom by Carol Apollonio

Featured Review Alisa Ganieva. Bride and Groom. Trans. Carol Apollonio. Dallas. Deep Vellum. 2017. 300 pages. From the first pages of her new novel, Alisa Ganieva toys with the expectations of her readers. Her title, Bride and Groom, seems to promise a traditional marriage narrative . Indeed, her main characters, a young man and woman who have each returned home from Moscow to “an outlying settlement ” near a big city in Dagestan and face pressure from their respective families to find a suitable match, initially seem to be playing stock parts familiar from romantic comedies. The young man’s parents have gambled and reserved a wedding hall at tremendous expense in the hope that the time pressure will help him buckle down and select a bride. The young woman fights off the overtures of a pedantic bore of a suitor and longs for true love and bigger horizons than those of the provincial, domestic world that threatens to consume her. Throughout the first half of her novel, Ganieva teases us, gradually drawing these two characters closer together and seemingly toward a traditional happy ending. Even early on, however, details in the background of the story hint at darker outcomes . The male protagonist is a human rights lawyer involved in investigating a murder case that recalls the killing of the Russian journalist Anna Politkovskaia (see WLT, Nov. 2011, 34–39); a local youth group stages a showy concert to agitate for the release of a corrupt local political boss blamed for multiple killings who has been tossed in jail; rival mosques divide World Literature in Review Julia Fiedorczuk’s poetic oxygen Verse, page 87 Arundhati Roy catalogs the disappeared Fiction, page 71 Eduardo Galeano’s urgent envoi Miscellaneous, page 93 68 WLT NOVEMBER–DECEMBER 2017 the town, leading to a conflict that seems likely to explode into mass violence at any moment. Grotesque details occasionally hint at a satiric purpose, but ultimately this is a tenser, sadder tale that underscores the horror and despair of post-Soviet life. Ganieva immerses us in a world where corruption and violence are so widespread and legal protections so meaningless that even love at first sight cannot guarantee a happy ending. Social pressures and empty traditions are all that seemingly remain of the fabric of society, and vestigial institutions from the Soviet period (cults of personality, political youth groups and meetings) have somehow macabrely become reanimated. In this unstable environment, Ganieva’s hero and heroine always seem at risk. Mundane choices—stepping away for a private conversation, agreeing to a date, any kind of nonconformity—can open the door for horrifying acts of violence that threaten to envelop not just the immediate target but also, as in the fable that a minor character tells Ganieva’s heroine at the beginning of the book, all of society. Politics and religion may represent the spark and excuse that sets off the conflagration, but the real issues are greed, corruption, and power—not faith. This is a timely novel for anyone who follows news from Russia, Chechnya, Dagestan, and other post-Soviet areas. It left me saddened and horrified because it offers a vivid portrait of a world where little place remains for private happiness and humane values. Strongly recommended. Emily D. Johnson University of Oklahoma Emily D. Johnson is an associate professor of Russian at the University of Oklahoma. She studies twentieth-century Russian literature and history and the legacy of the Stalinist labor camp system. Yale University Press published Gulag Letters, her translation of the correspondence of the Russo-Latvian poet Arsenii Formakov, in 2017. Fiction Carmen Maria Machado. Her Body and Other Parties: Stories. Minneapolis. Graywolf Press. 2017. 248 pages. Carmen Maria Machado’s debut shortstory collection, Her Body and Other Parties , reveals a new herald for the New Weird, marking Machado as one of the genre’s foremost voices alongside Caitlín R. Kiernan, China Miéville, and Jeff VanderMeer . Machado is also, indisputably, an anti-Lovecraft. Whereas Lovecraft—the brightest of the genre’s elder dark stars— abhorred the body, sex, and sexuality, and manifested his disgust through horrifying , polymorphic figures like Cthulhu and the shoggoths, Machado’s tales rejoice in the body and...

Long-term cilostazol administration ameliorates memory decline in senescence-accelerated mouse prone 8 (SAMP8) through a dual effect on cAMP and blood-brain barrier

Phosphodiesterases (PDEs), which hydrolyze and inactivate 3′, 5′-cyclic adenosine monophosphate (cAMP) and 3′, 5′-cyclic guanosine monophosphate (cGMP), play an important role in synaptic plasticity that underlies memory. Recently, several PDE inhibitors were assessed for their possible therapeutic efficacy in treating cognitive disorders. Here, we examined how cilostazol, a selective PDE3 inhibitor, affects brain functions in senescence-accelerated mouse prone 8 (SAMP8), an animal model of age-related cognitive impairment. Long-term administration of cilostazol restored the impaired context-dependent conditioned fear memory of SAMP8 to match that in normal aging control substrain SAMR1. Cilostazol also increased the number of cells containing phosphorylated cAMP-responsive element binding protein (CREB), a downstream component of the cAMP pathway. Finally, cilostazol improves blood-brain barrier (BBB) integrity, demonstrated by reduced extravasation of 2-deoxy-2-18F-fluoro-d-glucose and Evans Blue dye in the brains of SAMP8. This improvement in BBB integrity was associated with an increased amount of zona occludens protein 1 (ZO-1) and occludin proteins, components of tight junctions integral to the BBB. The results suggest that long-term administration of cilostazol exerts its beneficial effects on age-related cognitive impairment through a dual mechanism: by enhancing the cAMP system in the brain and by maintaining or improving BBB integrity.

Inhibition of phosphodiesterase 3, 4, and 5 induces endolymphatic hydrops in mouse inner ear, as evaluated with repeated 9.4T MRI

Conclusion: The data indicate important roles for phosphodiesterase (PDE) 3, 4, 5, and related cAMP and cGMP pools in the regulation of inner ear fluid homeostasis. Thus, dysfunction of these enzymes might contribute to pathologies of the inner ear.Objective: The mechanisms underlying endolymphatic hydrops, a hallmark of inner ear dysfunction, are not known in detail; however, altered balance in cAMP and cGMP signaling systems appears to be involved. Key components of these systems are PDEs, enzymes that modulate the amplitude, duration, termination, and specificity of cAMP and cGMP signaling.Method: To evaluate the role of PDE3, 4, and 5 and associated cAMP and cGMP pools in inner ear function, the effect of cilostamide (PDE3 inhibitor), rolipram (PDE4 inhibitor), and sildenafil (PDE5 inhibitor), administrated via mini-osmotic pumps, on mouse inner ear fluid homeostasis was evaluated using 9.4T in vivo MRI in combination with intraperitoneally administered Gadolinium contrast. Also, using human saccule as a model, the expression of PDEs and related signaling molecules and targets was studied using immunohistochemistry.Results: PDE3, PDE4, as well as PDE5 inhibitors resulted in the development of endolymphatic hydrops. Furthermore, PDE3B, PDE4D, and some related signaling components were shown to be expressed in the human saccule.

Zebrafish Melanophores: A Model for Teaching Second Messenger Systems.

A strong literature base supports the notion that active learning improves retention in the science classroom. To that end, a course was designed to allow students to develop their own experiments around a central biological question. The model system used in this particular course is control of melanosome dispersal via second messenger systems in zebrafish (Danio rerio) scales. Students start by applying agonists and antagonists to the cAMP and Ca(2+) second messenger systems, and then can progress to more refined questions with the model system. This project is advantageous because it could be easily adapted to fit the needs of many different courses and ability levels; it is relatively easy to perform; it is enjoyable to teach; and students can be largely given a free reign to decide upon the design of their experiments.

Prison Camp No. 29 for Prisoners of War from the Second World War on the Territory of Kazakhstan between 1943–1949

This article is the first publication of materials about Pakhta-Aral prison camp No. 29 for prisoners of war. The fate of prisoners of war (both Western and Eastern) remains largely unclear. One reason is because the camps for prisoners of war were subordinated to an extremely closed and classified structure - the GUPVI. To some extent, Pakhta-Aral was an untypical prison camp in the Soviet prison camp system. While most prison camps were established to support industry or resource extraction with labour, then a far smaller number of prison camps were connected to agriculture. The Pakhta-Aral camp was opened as a workforce supply for the cotton growing collective farms of Kazakhstan. Interestingly, archival data show that the need to supply the camp with food and clothes added some liberal aspects to camp life. Some researchers argue that prison camps were a model for the so-called 'non-Gulag' society, but the Pakhta-Aral camp shows that at least some civic practices were adopted where they helped to improve the functioning of the camp.

L’internement des Juifs en Italie et la géographie des camps (1940-1945)

The internment of the Jews in Italy and the geography of the campsItaly is among the nations that used concentration camps. As early as the 1930s, Italy built camps in Libya where close to 50 thousand civilian internees would go on to die. However, many years went by before historians became aware of this. This could perhaps be explained by the tendency to diminish Fascist crimes when faced with the generally much more horrifying crimes committed by the Nazis. This paper describes the Fascist concentration camp system and the different forms it took, whether in terms of the internees’ living conditions, the different camps’ specificities or the roundup and detention procedures. Civil internment came under the authority of the Ministry of the Interior, which managed a total of 48 camps until 1943. Up until then, Italian internment never exclusively targeted the Jews. Its goal was not extermination and it was not directly linked to the anti-Semitic laws enacted by the regime in 1938. However, beginning on November 30, 1943, the Italian internment under the Italian Social Republic’s collaborationist Fascist regime applied to all of the Jews. The internment used roughly 50 “provincial camps” and became a cog in the Holocaust machinery.

Archaeology, memory and history: the communist-era ruins at Galeşu / Nazarcea (on the Danube-Black sea canal trail)

The article presents the results of the archaeological research carried out in 2012, 2014 and 2015 at Galeşu/ Nazarcea (Poarta Albă commune, Constanţa County), in an area where, according to the information provided by several former political prisoners and locals, there once was a forced labour camp on the line of the Danube-Black Sea Canal. This endeavour started from the premise that the ruins of the former labour camp are part of the material memory of the communist concentration camp system and the period that followed, the archaeological research of which can contribute, along with other forms of memory (historical sources, memoirs, etc.), to a more nuanced understanding of a segment of Romania’s recent past. The main objective of the archaeological research was to unearth the memories contained by the site and the surrounding landscape. A preliminary study regarding the public gain from the valorisation of this material memory was also taken into consideration. The excavations in September 2014 have revealed a rectangular construction 25.20 m long and 7.80 m wide, with its inner space divided into several areas: a floor drain and traces of a cap from a washing unit (a sink, bathtub or shower), a brick floored room, a cellar, and a water reservoir. Another structure was excavated in October 2015. Of considerable dimensions (25x9 m), the building displays different characteristics. Eight sondages were made, from which the construction techniques were identified: foundation dumps filled with cement mixed with rocks, layered on a footing made from boulders of considerable dimensions, which became the base of the mortar held brick walls. The building had several inner walls. The floor layout was different, possibly in relation to the use of the rooms, with a board flooring, a thick layer of bitumen or an extremely brittle cement screed. On one of the long sides there were two entrances marked by access stairways. In the context of an existing slope, three of the corners of the building seem to have been consolidated through a system of stairs cast onto a pile of rocks. Other three sondages were made in order to check if a structure (C19) was indeed a building or a simple cone formed by collapsing earth. Along with these buildings other structures have been documented which belonged to the former labour camp, as well as the ruins of the subsequent period: industrial ruins, dikes, basins, enormous earth dumps, etc. To complete the data, information was collected from people living in the area, including a witness from the period the labour camp was in use. The moment of the construction and functioning period of the forced labour camp constitutes a prophetic time for the communist landscape that followed. Removing the apparently natural landscape, the archaeological research has documented the naked image of the modernist project – a secularized, anthropocentric Genesis whose existing claim is founded on the successive ruining of the different social engineering projects. Based on the obtained results we would like a more ample research and capitalization strategy to be adopted, which should include not only the former labour camp at Galeşu and its surroundings, but as many of the ruins associated to the project of building the Danube-Black Sea Canal as possible.

The Fragile Present: Statues Also Die with Night and Fog

Although the phrase le cinéma moderne is a leitmotif in midcentury French film criticism, the shapes and ambitions assigned to the modern aesthetic have remained difficult to pin down. My article positions this slippery term in relation to early work by two figures who have become emblematic of this postwar moment, Alain Resnais and Chris Marker. In exploring continuities between their reflection on African art under colonialism in the long-censored short Statues Also Die (1953) and the analysis of the Nazi camp system in their subsequent project Night and Fog (1956), I examine how an influential conception of cinematic modernity emerges from an associative practice that brings together images, issues, and moments in time. The modern here is the product of a montage-driven approach to form, but it also expresses anti-fascist political convictions that transcend the limits of the Second World War.

Next to Babi Yar: The Syrets Concentration Camp and the Evolution of Nazi Terror in Kiev

Drawing on the concept of the concentration camp, this examination of the history of the Syrets camp near Kiev traces the principle stages of Nazi terror, exploitation, and extermination in the occupied capital of the Ukraine. The author locates Syrets in the context of the evolving camp system of the Third Reich. The famous Soviet film director Aleksandr Dovzhenko, in Kiev for the first time after the Nazi occupation, wrote in his diary, struck me most of all, plunged me into unforgettable grief and despair, as well as anguish that I also will never forget, was the people. The people of Kiev. There were none. The city was empty. I saw only about one hundred in all, alone or in small groups. These were mainly old people and inva- lids, cripples. 1 Thus did Dovzhenko testify to the horrifying results of the Nazis' reign of terror in the capital of the Ukraine. But what were the instruments of this terror? What were its phases? How did these correspond to the general direction of Nazi policy in the occupied territories of the USSR as a whole? These questions have not received thorough consideration in the literature. Scholars have studied various aspects of the history of the Reichskommissariat Ukraine as a whole, German domina- tion in particular regions, or, regarding the district of Kiev, certain aspects of the op- pressive policy of the Nazi police and collaborationist formations. 2 Babi Yar has occupied a special place in the scholarship, but researchers have emphasized the shooting of the Jewish population of Kiev on September 28 and 29, 1941, while largely ignoring Nazi terror that lead up to this event and the genocidal mechanisms and measures that followed. 3 Here I analyze the history of the Syrets concentration camp as one of the chief instruments of Nazi terror in Kiev. The study focuses on events at Babi Yar too, though not so much on the shootings in late September 1941 as on events that preced- ed and followed them. Nazi terror evolved in Kiev, and the victims changed over time. Categorizing Syrets as a concentration camp requires explanation, particularly because European historiography usually reserves the term for those camps directly under the SS Concentration Camps Inspectorate of the Economic and Administrative Main Office (WVHA). 4 But this approach derives from the bureaucratic definition

Before Auschwitz: Jewish prisoners in the prewar concentration camps

Auschwitz—the largest and most notorious of Hitler’s concentration camps—was founded in 1940, but the Nazis had been detaining Jews in camps ever since they came to power in 1933. Before Auschwitz unearths the little-known origins of the concentration camp system in the years before World War II and reveals the instrumental role of these extralegal detention sites in the development of Nazi policies toward Jews and in plans to create a racially pure Third Reich. Investigating more than a dozen camps, from the infamous Dachau, Buchenwald, and Sachsenhausen to less familiar sites, Kim Wunschmann uncovers a process of terror meant to identify and isolate German Jews in the period from 1933 to 1939. The concentration camp system was essential to a regime then testing the limits of its power and seeking to capture the hearts and minds of the German public. Propagandized by the Nazis as enemies of the state, Jews were often targeted for arbitrary arrest and then routinely subjected to the harshest treatment and most punishing labor assignments in the camps. Some of them were murdered. Over time, shocking accounts of camp life filtered into the German population, sending a message that Jews were different from true Germans: they were portrayed as dangerous to associate with and fair game for acts of intimidation and violence. Drawing on a wide range of previously unexplored archives, Before Auschwitz explains how the concentration camps evolved into a universally recognized symbol of Nazi terror and Jewish persecution during the Holocaust.

Study on mechanism for anti-depression efficacy of Sini San through auxiliary mechanism elucidation system for Chinese medicine

As regulating the function of the liver and spleen of the famous traditional formula, Sini San is widely used in the treatment of various diseases caused by liver depression and Qi stagnation, and its efficacy is significant clinically. Recently it is discovered that Sini San is effective in the treatment of nervous system diseases such as depression. Furthermore, there is a lot of literature about the effect of Sini San on the molecular mechanism of antidepressant. However, the anti-depression mechanism of Sini San is not very clear, in our present study, based on the auxiliary mechanism elucidation system for Chinese medicine and network pharmacology system to construct the chemical ingredients of the target interactions and disease-related protein of the interaction network. Results show that there are 263 chemical ingredients and 19 corresponding targets of depression in Sini San network. Sini San can anti-depressant effect through G-protein coupled receptor protein signaling pathway, cAMP system, neurological system process and neurotransmitter secretion, inflammatory response, neuroendocrine, metal ion transport and so on. These studies provided valuable clues for the mechanism and treatment of anti-depressant.

No Total Totality: Forced Labor, Stalinism, and De-Stalinization

Alan Barenberg, Gulag Town, Company Town: Forced Labor and Its Legacy in Vorkuta. 331 pp. New Haven: Yale University Press, 2014. ISBN-13 9780300179446. $65.00. Anatolii I. Shirokov, Dal'stroi v sotsial'no-ekonomicheskom razvitii SeveroVostokaSSSR (1930-1950-egg.) (Dal 'stroi in the Socioeconomic Development of the Northeastern USSR [1930-1950s]). 654 pp. Moscow: Rosspen, 2014. ISBN-13 978-5824318944. Aleksei V. Zakharchenko, NKVD iformirovanieaviapromyshlennogo kompleksa v Povolzh 'e, 1940-1943 (The NKVD and the Formation of the Aviation Industrial Complex in the Volga Region, 1940-43). 480 pp. Samara: Institut rossiiskoi istorii Rossiiskoi akademii nauk, Povolzhskii filial, 2013. ISBN 978-5934246588. Recent historical writing about the Soviet Union includes notable, muchneeded, and diligent works dedicated to the consolidation, development, and expansion of the prison camp system, as well as the role that it played in the Soviet Union's transition from a dictatorship to an ordinary authoritarian regime. Researchers have made use of new sources to produce valuable work examining the deep internal conditions leading to the expansion of the I Gulag. (1) The books under review are vivid examples of this historiographical trend. Descriptions of the camps and their economic structures, as well as summaries of statistical evidence about the number of prisoners and industrial output--characteristic of earlier Gulag research--are not completely absent from these new works, but they have taken on a secondary role. To a much greater degree, the authors focus on the practices of administering the camp economy and realizing departmental interests; the evolution of inmate society; and implicit or explicit signs of crisis in the Stalinist system of forced labor. Alan Barenberg dedicates his brilliantly written book to the largest division of the Gulag: the camp complex of Vorkuta, in the northern European part of the USSR. The region, ill-suited for habitation but rich in resources (primarily coal), was the ideal place for a Stalinist camp. Vorkuta became the symbol of the camp system for these and many other reasons. After the camp was eliminated, it became an informative example of how the Gulag's economic and social structures evolved and were maintained. Equally emblematic is Anatolii I. Shirokov's subject of study: the notorious Dal'stroi Trust, which mined gold from the rich deposits on the Kolyma river basin in the northeastern USSR. Over a quarter-century (1932-56), the basin yielded 1,200 tons of gold and huge amounts of other nonferrous metals. Around 850,000 prisoners passed through the camps at Kolyma from 1932 to 1953, of whom 120,000 died (482, 638). Aleksei Zakharchenko focuses his study on a lesser-known and smaller, though no less significant, site of Stalinist forced labor. The famous airplane factories near Kuibyshev, which were constructed by prisoners in extreme conditions in compressed time frames, played a significant role in the war with Nazi Germany, supplying the front with a large portion of its Soviet planes. Despite thematic differences, each of these three works analyzes the same phenomenon: the formation, development, and expansion of major production complexes under the direction of the People's Commissariat of Internal Affairs, later Ministry of Internal Affairs (NKVD-MVD USSR). (2) I am grateful to Liudmila Novikova, Victoria Frede, Paul Werth, and Rhiannon Dowling for their valuable comments and skillful translation. This article was prepared within the framework of a subsidy granted to the National Research University Higher School of Economics (HSE) by the government of the Russian Federation for the implementation of the Global Competitiveness Program. The authors examine two models of Gulag expansion: the first through camp colonization of distant and hard-to-reach parts of the country; and the second through the use of forced labor in populated regions of substantial economic value. …