bluuebunny/crossref_metadata_2025 huggingface dataset:
Congressional Seat Swings: Revisiting Exposure in House Elections
Authors: Gaddie Ronald Keith
Published: January 2007

Oppenheimer, Stimson, and Waterman's exposure thesis of partisan change contends that shifts in the partisan composition of Congress are related to the long-term stability of the electoral system. Applying their exposure model to elections from 1962-1994 produces seat change estimates that generally follow the actual data pattern, but these estimates produce large predictive errors. When the exposure model is reestimated using data from 1962-1994, exposure is not significantly related to partisan seat swings. This article advances a seat change model that relies on an alter nate measure of exposure: the net exposure of the president's party in open seats. Open-seat exposure is significantly related to the partisan seat swing, and substantially improves on the economic evaluation/surge and-decline/ exposure model of seat change. In an era of high incumbent security and strategic retirement from Congress, the balance of open seats is a better indicator of partisan vulnerability, and better reflects the nature of partisan exposure.
Balance of Power and System Stability: Simulating Complex Anarchical Environments Over the Internet
Authors: Van Belle Douglas A.
Published: January 2007

Game theoretic examinations of balance of power hypotheses in the context of N-player games have identified certain distributions of resources which should lead to system stability, defined as the continued survival of all participants (Wagner 1986, Niou, Ordeshook, and Rose 1989; Niou and Ordeshook 1990). This article uses data from a seven-player simula tion of realist international politics to analyze hypotheses on power dis tributions, the number of actors, and system stability By conducting the simulation over the Internet, a tremendous number of runs through the simulation can be completed in a relatively short time, thereby generat ing sufficient data for the statistical analysis of the distributions of power that occur. These data can then be used to examine how those distribu tions relate to the number of participants found in the eventual end-state of the system.
Regime Changes and Interstate Conflict, 1816-1992
Authors: Enterline Andrew J.
Published: January 2007

Are domestic regime changes catalysts for interstate conflict? How does this relationship vary across different types of regime change? Do regime changes affect the vulnerability and aggressiveness of states equally in foreign policy? I investigate these questions using pooled data identifying three categories of regime change and militarized interstate conflict be havior for 171 states for the period 1816-1992. Specifically, I estimate the effects of regime changes on dispute and war initiation and target behavior during the first 15 years of the new regime's existence for two sample periods, 1816-1992 and 1946-1992. The analyses consistently demonstrate a strong link between autocratization and dispute initiation, and a less robust relationship between autocratization and war initiation. New autocratic regimes and dispute targets are positively related, though this link is contingent upon the operationalization of the dependent vari able. Autocratization and war target are negatively related when the de pendent variable is non-revisionism. Lastly, the analyses consistently suggest that new democracies are not more dispute or war prone, either as initiator or target.
Do Attitudes Toward Specific Supreme Court Decisions Matter? The Impact of Webster and Texas v. Johnson on Public Confidence in the Supreme Court
Authors: Grosskopf Anke , Mondak Jeffery J.
Published: January 2007

In this article, we revisit the question of whether, and in what manner, attitudes regarding specific Supreme Court decisions influence subsequent levels of confidence in the Court itself. Analysis centers on the impact of the 1989 Webster abortion decision and Texas v. Johnson, the flag-burning edict released immediately prior to Webster. Using data from three Harris polls, one conducted just before the two decisions, and two conducted soon after, we design a quasi-experimental test in which data are ana lyzed using ordered logistic regression. Results demonstrate that agree ment with the rulings did affect perceptions of the Court, and that the pattern of effects is indicative of a negativity bias; that is, disagreement with one or both decisions substantially reduced confidence in the Court, but agreement with both edicts brought only a marginal gain in confi dence. Results also reveal that these effects did not decay in strength from the time of the first postdecision poll (conducted immediately after the decisions were released) to the time of the second postdecision poll (con ducted six weeks later).
Wielding the Stick Instead of the Carrot: Labor PAC Punishment of Pro-NAFTA Democrats
Authors: Engel Steven T. , Jackson David J.
Published: January 2007

Political action committees normally use contributions as a reward or inducement for access or favorable roll-call votes. In extreme cases, how ever, PACs may reduce funding as part of a punishment strategy. The roll- call vote on the North American Free Trade Agreement in the House of Representatives provides an interesting test case for the strategy of pun ishment. Organized labor was clearly against NAFTA and threatened to reduce support to proponents of the agreement. If a punishment strategy is followed by interest groups, we would expect to find it in this case. Ordinary least squares regression is used to examine labor PAC contribu tion strategy. We find that labor followed a short-term punishment strat egy against Democratic supporters of NAFTA.
State Responses to National Demnocratic Party Reform
Authors: Walz Jeffrey S. , Comer John
Published: January 2007

This research examines the proliferation of Democratic state presidential preference primaries from 1972-80, an unintended consequence of McGovern-Fraser reforms to delegate selection adopted following the acrimonious 1968 Democratic National Convention. Unlike previous work, which has addressed the primary proliferation qualitatively and in a way that does not permit sorting out the various elements that may underlie the adoption of party reforms in the 1970s, we operationalize and test hypotheses about the influence of several factors -Democratic National Committee directives, party strength and type, partisan control of state government, home-state candidates, and divisive caucuses -on states moving from a caucus/convention arrangement of selecting delegates to a presidential preference primary. Our findings suggest that both national party efforts to involve more rank and file in the process and state characteristics predisposed some states to move in the direction of a preference primary rather than continuing with a party caucus/convention. Democratic control of state government, the presence of home-state candidates, and noncompliance with DNC directives were the most powerful forces behind states adopting Democratic presidential preference primaries.
From the Inner Ring Out: News Congruence, Cue-Taking, and Campaign Coverage
Authors: Shaw Daron R. , Sparrow Bartholomew H.
Published: January 2007

Studies of the organizational and behavioral characteristics of the American news media, as well as studies of media effects, often presume a basic institutional unity among news organizations. These studies typically analyze a small set of prestige media, and then make or infer conclusions with respect to the non-prestige media or the news media in general. The intention here is to verify empirically the extent to which the non-prestige ”outer ring” media in fact take cues from the prestige ”inner ring” news organizations. Using content analyses of forty-one daily newspapers from the 1992 presidential election campaign, we find that the outer ring newspapers sometimes replicate the issue agenda of the inner ring newspapers, but that they exercise significant discretion with respect to the favorability of their coverage of the presidential candidates and specific issues.
The Partisan Component to the Incumbency Advantage: 1956-1996
Authors: Lockerbie Brad
Published: January 2007

The power of incumbency in congressional elections is widely accepted. Is there a partisan component to the incumbency advantage? The theories of divided government push in two directions. Jacobson's argument would lead one to believe that the Democrats should be advantaged. Fiorina's argument would lead one to believe that there should be no difference between the parties. Using the American National Election Studies of 1956 through 1996, one can see that there is little difference in the two parties' abilities to capitalize on the advantages incumbency confers. Both parties' incumbent members of the House seem to provide the particularized services that both Jacobson and Fiorina think are so important for retaining a seat in the House. Also, constituents view both parties' incumbents as being equally responsive on matters of public policy. Consequently, there is little reason to fear that the policymaking process is distorted by one party being more advantaged by incumbency than another. Last, the evidence, albeit indirect, lends support to the policy-balancing model of Fiorina.
Derailing Presidential Fast-Track Authority: The Impact of Constituency Pressures and Political Ideology on Trade Policy in Congress
Authors: Conley Richard S.
Published: January 2007

This article explores the relative impact of constituency, political ideology, and labor strength on support for presidential fast-track trade authority in 1991 and 1997. Multivariate logistic regression analysis of legislators' positions shows that constituency factors have increased in importance while political ideology explains less of the variation in support for fast-track over time. The stronger constituency basis of legislators' positions reflects both the impact of NAFTA on Democrats' stances toward free trade and the growing divide among Republicans on trade issues. Future presidential bids for fast-track authority must center on specific trade agreements and will require grassroots support to surmount congressional opposition.
Yet more American circulating libraries: a preliminary checklist of Brooklyn (New York) circulating libraries
Authors: Croteau Jeffrey
Published: December 2006

Builds on earlier work, by David Kaser, on circulating libraries in America in the eighteenth and nineteenth centuries. A brief introduction to the history of circulating libraries in America is followed by a study of such libraries in the specific context of Brooklyn (New York) and its socio-economic development. Drawing on a variety of primary sources, including library catalogues and local newspapers and directories, a checklist of thirty-three circulating libraries in Brooklyn, in between 1809 and 1896, is assembled, accompanied by commentary based on primary evidence. The list adds considerably to our knowledge of circulating libraries in Brooklyn (Kaser having identified just two libraries in his earlier work), as well as to our understanding of this important, yet often ephemeral, cultural institution.
Reframing Arcimboldo's 'Librarian'
Authors: Elhard K. C.
Published: December 2006

Giuseppe Arcimboldo's The librarian ( ca. 1566), an illusionary painting of a man made out of books, has traditionally been interpreted as an amusing caricature of the Hapsburg court historiographer Wolfgang Lazius. However, given the formal similarities between 'The librarian' and the illustration of the book fool in Sebastian Brant's famous Ship of fools (Narrenschiff, 1494), it is likely that contemporary viewers associated the painting with Brant's satire of slothfully ignorant book collectors. This paper employs The librarian 's similarities to the character of the book fool as a starting point for a reexamination of the painting's significance. Building on my previous discussion of the painting, I present new avenues of enquiry involving texts such as the 'Philobiblon' ( The love of books, 1345) by Richard de Bury, Bishop of Durham, as well as Reformation imagery and the context of the Hapsburg court. Viewing the painting through the framework of other literary and artistic works, this essay begins to conceptually 'reframe' the painting within the larger context of the artist's cultural milieu.
Traces of Russian Libraries in China
Authors: Gamsa Mark
Published: December 2006

The libraries described and discussed in this article were formed, during the first half of the twentieth century, by readers of Russian in China, and in particular by the Russian-speaking community in Harbin, the centre of Russian settlement and emigration in Manchuria (presently North-east China). The article is a revised and augmented version of a paper presented at the panel on 'Russian Far Eastern Publications in Exile', VII World Congress of the International Council for Central and East European Studies (ICCEES) in Berlin, 29 July 2005.
The Bradford Library and Literary Society, 1774–1980
Authors: Roberts Daphne , Duckett Bob
Published: December 2006

Examines the history of the proprietary Bradford Library and Literary Society over two centuries following its establishment in 1774 as a major cultural institution for the town's prosperous middle classes. Describes and discusses the institution's locations, its membership, finances, regulatory arrangements, as well as the contributions of its librarians and the complexion of its book stock, book loans and book selection.
Trapping and apoptosis of novel subsets of memory T lymphocytes expressing CCR6 in the spleen of HIV-infected patients
Authors: Lécureuil Cédric , Combadière Béhazine , Mazoyer Elodie , Bonduelle Olivia , Samri Assia , Autran Brigitte , Debré Patrice , Combadière Christophe
Published: December 2006

CCR6, a homeostatic chemokine receptor, is shown here to characterize subsets of both central and effector memory T cells that secrete high levels of IL-2 and TNF-α in response to polyclonal and antigen-specific stimulation. CCR6+ T lymphocytes disappeared dramatically from the peripheral blood of HIV-infected patients as HIV disease progressed. The capacity of CD4+CCR6+ to secrete multiple cytokines remained intact among HIV-infected long-term nonprogressors but was partially lost from subjects with standard disease progression. CCR6+ T lymphocytes, regardless of their CCR7 expression, accumulated in the spleen of HIV-infected patients, where they died by apoptosis. Assessment of CCR6 expression allowed us to describe novel memory T-cell subpopulations capable of high cytokine production and provided evidence of a pathologic CCR6-dependent pathway of memory T-cell homing that may participate in the loss of memory response against infections.
Polymorphisms in DNA repair genes and therapeutic outcomes of AML patients from SWOG clinical trials
Authors: Kuptsova Nataliya , Kopecky Kenneth J. , Godwin John , Anderson Jeanne , Hoque Ashraful , Willman Cheryl L. , Slovak Marilyn L. , Ambrosone Christine B.
Published: December 2006

Repair of damage to DNA resulting from chemotherapy may influence drug toxicity and survival in response to treatment. We evaluated the role of polymorphisms in DNA repair genes APE1, XRCC1, ERCC1, XPD, and XRCC3 in predicting therapeutic outcomes of older adults with acute myeloid leukemia (AML) from 2 Southwest Oncology Group (SWOG) clinical trials. All patients received standard chemotherapy induction regimens. Using logistic and proportional hazards regression models, relationships between genotypes, haplotypes, and toxicities, response to induction therapy, and overall survival were evaluated. Patients with XPD Gln751C/Asp312G (‘D’) haplotype were more likely to have complete response (OR = 3.06; 95% CI, 1.44-6.70) and less likely to have resistant disease (OR = 0.32; 95%CI, 0.14-0.72) than patients with other haplotypes. ERCC1 polymorphisms were significantly associated with lung (P = .037) and metabolic (P = .041) toxicities, and patients with the XRCC3 241Met variant had reduced risk of liver toxicity (OR = 0.32; 95%CI, 0.11-0.95). Significant associations with other toxicities were also found for variant XPD genotypes/haplotypes. These data from clinical trials of older patients treated for AML indicate that variants in DNA repair pathways may have an impact on both outcomes of patients and toxicities associated with treatments. With validation of results in larger samples, these findings could lead to optimizing individual chemotherapy options.
MALT lymphoma and extranodal diffuse large B-cell lymphoma are targeted by aberrant somatic hypermutation
Authors: Deutsch Alexander J. A. , Aigelsreiter Ariane , Staber Philipp B. , Beham Alfred , Linkesch Werner , Guelly Christian , Brezinschek Ruth I. , Fruhwirth Margareta , Emberger Werner , Buettner Maike , Beham-Schmid Christine , Neumeister Peter
Published: December 2006

Recently, a novel mechanism introducing genetic instability, termed aberrant somatic hypermutation (ASHM), has been described in diffuse large B-cell lymphoma. To further investigate whether ASHM also occurs in mucosa-associated lymphoid tissue type (MALT) lymphoma, we studied the mutation profile of PIM1, PAX5, RhoH/TTF, and c-MYC in 17 MALT lymphomas and 17 extranodal diffuse large B-cell lymphomas (DLBCLs) still exhibiting a low-grade MALT lymphoma component (transformed MALT lymphoma). Mutations in one or more genes were detected in 13 (76.5%) of 17 cases of MALT lymphomas and in all of 17 (100%) cases of extranodal DLBCL. A total of 100 sequence variants were found in 30 of 34 cases, 28 in the MALT lymphomas and 72 in extranodal DLBCL. Further, in PIM1 and c-MYC some of the mutations were found to affect coding exons, leading to amino acid exchanges, thus potentially altering gene function. Expression levels of activation-induced cytidine deaminase (AID), an enzyme essential for somatic hypermutation (SHM), was associated with the mutational load. These data indicate that aberrant SHM is associated with extranodal DLBCL and MALT lymphoma, likewise. By mutating regulatory and coding sequences of the targeted genes, ASHM may represent a major contributor to their pathogenesis.
Oridonin, a diterpenoid extracted from medicinal herbs, targets AML1-ETO fusion protein and shows potent antitumor activity with low adverse effects on t(8;21) leukemia in vitro and in vivo
Authors: Zhou Guang-Biao , Kang Hui , Wang Lan , Gao Li , Liu Ping , Xie Jun , Zhang Feng-Xiang , Weng Xiang-Qin , Shen Zhi-Xiang , Chen Jue , Gu Long-Jun , Yan Ming , Zhang Dong-Er , Chen Sai-Juan , Wang Zhen-Yi , Chen Zhu
Published: December 2006

Studies have documented the potential antitumor activities of oridonin, a compound extracted from medicinal herbs. However, whether oridonin can be used in the selected setting of hematology/oncology remains obscure. Here, we reported that oridonin induced apoptosis of t(8;21) acute myeloid leukemic (AML) cells. Intriguingly, the t(8;21) product AML1-ETO (AE) fusion protein, which plays a critical role in leukemogenesis, was degraded with generation of a catabolic fragment, while the expression pattern of AE target genes investigated could be reprogrammed. The ectopic expression of AE enhanced the apoptotic effect of oridonin in U937 cells. Preincubation with caspase inhibitors blocked oridonin-triggered cleavage of AE, while substitution of Ala for Asp at residues 188 in ETO moiety of the fusion abrogated AE degradation. Furthermore, oridonin prolonged lifespan of C57 mice bearing truncated AE-expressing leukemic cells without suppression of bone marrow or reduction of body weight of animals, and exerted synergic effects while combined with cytosine arabinoside. Oridonin also inhibited tumor growth in nude mice inoculated with t(8;21)-harboring Kasumi-1 cells. These results suggest that oridonin may be a potential antileukemia agent that targets AE oncoprotein at residue D188 with low adverse effect, and may be helpful for the treatment of patients with t(8;21) AML.
Endorepellin, the C-terminal angiostatic module of perlecan, enhances collagen-platelet responses via the α2β1-integrin receptor
Authors: Bix Gregory , Iozzo Rex A. , Woodall Ben , Burrows Michelle , McQuillan Angela , Campbell Shelly , Fields Gregg B. , Iozzo Renato V.
Published: December 2006

Endorepellin, a C-terminal fragment of the vascular basement membrane proteoglycan perlecan, inhibits angiogenesis via the α2β1-integrin receptor. Because this integrin is also implicated in platelet-collagen responses and because endorepellin or its fragments are generated in response to injury and inflammation, we hypothesized that endorepellin could also affect platelet biology. We discovered that endorepellin supported α2β1-dependent platelet adhesion, without appreciably activating or aggregating platelets. Notably, endorepellin enhanced collagen-evoked responses in platelets, in a src kinase-dependent fashion, and enhanced the collagen-inhibitory effect of an α2β1-integrin function-blocking antibody. Collectively, these results suggest that endorepellin/α2β1-integrin interaction and effects are specific and dependent on cell type, differ from those emanated by exposure to collagen, and may be due to cellular differences in α2β1-integrin activation/ligand affinity state. These studies also suggest a heretofore unrecognized role for angiostatic basement membrane fragments in platelet biology.
RNA silencing of the mitochondrial ABCB7 transporter in HeLa cells causes an iron-deficient phenotype with mitochondrial iron overload
Authors: Cavadini Patrizia , Biasiotto Giorgio , Poli Maura , Levi Sonia , Verardi Rosanna , Zanella Isabella , Derosas Manuela , Ingrassia Rosaria , Corrado Marcella , Arosio Paolo
Published: December 2006

X-linked sideroblastic anemia with ataxia (XLSA/A) is caused by defects of the transporter ABCB7 and is characterized by mitochondrial iron deposition and excess of protoporphyrin in erythroid cells. We describe ABCB7 silencing in HeLa cells by performing sequential transfections with siRNAs. The phenotype of the ABCB7-deficient cells was characterized by a strong reduction in proliferation rate that was not rescued by iron supplementation, by evident signs of iron deficiency, and by a large approximately 6-fold increase of iron accumulation in the mitochondria that was poorly available to mitochondrial ferritin. The cells showed an increase of protoporphyrin IX, a higher sensitivity to H2O2 toxicity, and a reduced activity of mitochondrial superoxide dismutase 2 (SOD2), while the activity of mitochondrial enzymes, such as citrate synthase or succinate dehydrogenase, and ATP content were not decreased. In contrast, aconitase activity, particularly that of the cytosolic, IRP1 form, was reduced. The results support the hypothesis that ABCB7 is involved in the transfer of iron from mitochondria to cytosol, and in the maturation of cytosolic Fe/S enzymes. In addition, the results indicate that anemia in XLSA/A is caused by the accumulation of iron in a form that is not readily usable for heme synthesis.
A leukemia fusion protein attenuates the spindle checkpoint and promotes aneuploidy
Authors: Boyapati Anita , Yan Ming , Peterson Luke F. , Biggs Joseph R. , Le Beau Michelle M. , Zhang Dong-Er
Published: December 2006

The 8;21 chromosomal translocation occurs in 15% to 40% of patients with the FAB M2 subtype of acute myeloid leukemia (AML). This chromosomal abnormality fuses part of the AML1/RUNX1 gene to the ETO/MTG8 gene and generates the AML1-ETO protein. We previously identified a C-terminal truncated AML1-ETO protein (AEtr) in a mouse leukemia model. AEtr is almost identical to the AML1-ETO exon 9a isoform expressed in leukemia patients. Here, we describe a novel function of AEtr in the development of aneuploidy through spindle checkpoint attenuation. AEtr cells had a reduced mitotic index following nocodazole treatment, suggesting a failure in a subset of cells to arrest in mitosis with a functional spindle checkpoint. Additionally, primary leukemia cells and cell lines expressing AEtr were aneuploid. Moreover, AEtr cells had reduced levels of several spindle checkpoint proteins including BubR1 and securin following treatment with the spindle poison nocodazole. These results suggest that inactivation of the spindle checkpoint may contribute to the development of aneuploidy described in t(8;21) leukemia patients.
Mast cell–derived TNF can promote Th17 cell–dependent neutrophil recruitment in ovalbumin-challenged OTII mice
Authors: Nakae Susumu , Suto Hajime , Berry Gerald J. , Galli Stephen J.
Published: December 2006

Both mast cells and IL-17 can contribute to host defense and pathology in part by orchestrating neutrophil recruitment, but the possible role of mast cells in IL-17–induced inflammation remains to be defined. We found that mast cells and IL-17, but neither IFN-γ nor FcRγ signaling, contributed significantly to the antigen (Ag)–dependent airway neutrophilia elicited in ovalbumin-specific T-cell receptor (TCR)–expressing C57BL/6-OTII mice, and that IFN-γ significantly suppressed IL-17–dependent airway neutrophilia in this setting. IL-18, IL-1β, and TNF each contributed significantly to the development of Ag- and T helper 17 (Th17 cell)–mediated airway neutrophilia. Moreover, IL-17 enhanced mast cell TNF production in vitro, and mast cell–associated TNF contributed significantly to Ag- and Th17 cell–mediated airway neutrophilia in vivo. By contrast, we detected no significant role for the candidate mediators histamine, PGD2, LTB4, CXCL10, or IL-16, each of which can be produced by mast cells and other cell types, in the neutrophil infiltration elicited in this model. These findings establish that mast cells and mast cell–derived TNF can significantly enhance, by FcRγ-independent mechanisms, the Ag- and Th17 cell–dependent development of a neutrophil-rich inflammatory response at a site of Ag challenge.
Granulocyte colony-stimulating factor enhances bone tumor growth in mice in an osteoclast-dependent manner
Authors: Hirbe Angela C. , Uluçkan Özge , Morgan Elizabeth A. , Eagleton Mark C. , Prior Julie L. , Piwnica-Worms David , Trinkaus Kathryn , Apicelli Anthony , Weilbaecher Katherine
Published: December 2006

Inhibition of osteoclast (OC) activity has been associated with decreased tumor growth in bone in animal models. Increased recognition of factors that promote osteoclastic bone resorption in cancer patients led us to investigate whether increased OC activation could enhance tumor growth in bone. Granulocyte colony-stimulating factor (G-CSF) is used to treat chemotherapy-induced neutropenia, but is also associated with increased markers of OC activity and decreased bone mineral density (BMD). We used G-CSF as a tool to investigate the impact of increased OC activity on tumor growth in 2 murine osteolytic tumor models. An 8-day course of G-CSF alone (without chemotherapy) significantly decreased BMD and increased OC perimeter along bone in mice. Mice administered G-CSF alone demonstrated significantly increased tumor growth in bone as quantitated by in vivo bioluminescence imaging and histologic bone marrow tumor analysis. Short-term administration of AMD3100, a CXCR4 inhibitor that mobilizes neutrophils with little effect on bone resorption, did not lead to increased tumor burden. However, OC-defective osteoprotegerin transgenic (OPGTg) mice and bisphosphonate-treated mice were resistant to the effects of G-CSF administration upon bone tumor growth. These data demonstrate a G-CSF–induced stimulation of tumor growth in bone that is OC dependent.
Iron chelation regulates cyclin D1 expression via the proteasome: a link to iron deficiency–mediated growth suppression
Authors: Nurtjahja-Tjendraputra Effie , Fu Dong , Phang Juanita M. , Richardson Des R.
Published: December 2006

Iron (Fe) plays an important role in proliferation, and Fe deficiency results in G1/S arrest. Despite this, the precise role of Fe in cell-cycle control remains unclear. Cyclin D1 plays a critical function in G1 progression by interacting with cyclin-dependent kinases. Previously, we examined the effect of Fe depletion on the expression of cell-cycle control molecules and identified a marked decrease in cyclin D1 protein, although the mechanism involved was unknown. In this study, we showed that cyclin D1 was regulated posttranscriptionally by Fe depletion. Iron chelation of cells in culture using desferrioxamine (DFO) or 2-hydroxy-1-naphthylaldehyde isonicotinoyl hydrazone (311) decreased cyclin D1 protein levels after 14 hours and was rescued by the addition of Fe. Cyclin D1 half-life in control cells was 80 ± 15 minutes (n = 5), while in chelator-treated cells it was significantly (P < .008) decreased to 38 ± 3 minutes (n = 5). Proteasomal inhibitors rescued the Fe chelator–mediated decrease in cyclin D1 protein, suggesting the role of the proteasome. In Fe-replete cells, cyclin D1 was degraded in an ubiquitin-dependent manner, while Fe depletion induced a ubiquitin-independent pathway. This is the first report linking Fe depletion–mediated growth suppression at G1/S to a mechanism inducing cyclin D1 proteolysis.
New differentiation pathway for double-negative regulatory T cells that regulates the magnitude of immune responses
Authors: Zhang Dong , Yang Wei , Degauque Nicolas , Tian Yan , Mikita Allison , Zheng Xin Xiao
Published: December 2006

Recent studies have demonstrated that in peripheral lymphoid tissues of normal mice and healthy humans, 1% to 5% of αβ T-cell receptor–positive (TCR+) T cells are CD4−CD8− (double-negative [DN]) T cells, capable of down-regulating immune responses. However, the origin and developmental pathway of DN T cells is still not clear. In this study, by monitoring CD4 expression during T-cell proliferation and differentiation, we identified a new differentiation pathway for the conversion of CD4+ T cells to DN regulatory T cells. We showed that the converted DN T cells retained a stable phenotype after restimulation and that furthermore, the disappearance of cell-surface CD4 molecules on converted DN T cells was a result of CD4 gene silencing. The converted DN T cells were resistant to activation-induced cell death (AICD) and expressed a unique set of cell-surface markers and gene profiles. These cells were highly potent in suppressing alloimmune responses both in vitro and in vivo in an antigen-specific manner. Perforin was highly expressed by the converted DN regulatory T cells and played a role in DN T-cell–mediated suppression. Our findings thus identify a new differentiation pathway for DN regulatory T cells and uncover a new intrinsic homeostatic mechanism that regulates the magnitude of immune responses. This pathway provides a novel, cell-based, therapeutic approach for preventing allograft rejection.
MMP-2, MT1-MMP, and TIMP-2 are essential for the invasive capacity of human mesenchymal stem cells: differential regulation by inflammatory cytokines
Authors: Ries Christian , Egea Virginia , Karow Marisa , Kolb Helmut , Jochum Marianne , Neth Peter
Published: December 2006

Human mesenchymal stem cells (hMSCs) represent promising tools in various clinical applications, including the regeneration of injured tissues by endogenous or transplanted hMSCs. The molecular mechanisms, however, that control hMSC mobilization and homing which require invasion through extracellular matrix (ECM) barriers are almost unknown. We have analyzed bone marrow–derivedhMSCs and detected strong expression and synthesis of matrix metalloproteinase 2 (MMP-2), membrane type 1 MMP (MT1-MMP), tissue inhibitor of metalloproteinase 1 (TIMP-1), and TIMP-2. The ability of hMSCs to traverse reconstituted human basement membranes was effectively blocked in the presence of synthetic MMP inhibitors. Detailed studies by RNA interference revealed that gene knock-down of MMP-2, MT1-MMP, or TIMP-2 substantially impaired hMSC invasion, whereas silencing of TIMP-1 enhanced cell migration, indicating opposing roles of both TIMPs in this process. Moreover, the inflammatory cytokines TGF-β1, IL-1β, and TNF-α up-regulated MMP-2, MT1-MMP, and/or MMP-9 production in these cells, resulting in a strong stimulation of chemotactic migration through ECM, whereas the chemokine SDF-1α exhibited minor effects on MMP/TIMP expression and cell invasion. Thus, induction of specific MMP activity in hMSCs by inflammatory cytokines promotes directed cell migration across reconstituted basement membranes in vitro providing a potential mechanism in hMSC recruitment and extravasation into injured tissues in vivo.
Alternative splicing and differential gene expression in colon cancer detected by a whole genome exon array
Authors: Gardina Paul J , Clark Tyson A , Shimada Brian , Staples Michelle K , Yang Qing , Veitch James , Schweitzer Anthony , Awad Tarif , Sugnet Charles , Dee Suzanne , Davies Christopher , Williams Alan , Turpaz Yaron
Published: December 2006

Background

Alternative splicing is a mechanism for increasing protein diversity by excluding or including exons during post-transcriptional processing. Alternatively spliced proteins are particularly relevant in oncology since they may contribute to the etiology of cancer, provide selective drug targets, or serve as a marker set for cancer diagnosis. While conventional identification of splice variants generally targets individual genes, we present here a new exon-centric array (GeneChip Human Exon 1.0 ST) that allows genome-wide identification of differential splice variation, and concurrently provides a flexible and inclusive analysis of gene expression.

Results

We analyzed 20 paired tumor-normal colon cancer samples using a microarray designed to detect over one million putative exons that can be virtually assembled into potential gene-level transcripts according to various levels of prior supporting evidence. Analysis of high confidence (empirically supported) transcripts identified 160 differentially expressed genes, with 42 genes occupying a network impacting cell proliferation and another twenty nine genes with unknown functions. A more speculative analysis, including transcripts based solely on computational prediction, produced another 160 differentially expressed genes, three-fourths of which have no previous annotation. We also present a comparison of gene signal estimations from the Exon 1.0 ST and the U133 Plus 2.0 arrays.

Novel splicing events were predicted by experimental algorithms that compare the relative contribution of each exon to the cognate transcript intensity in each tissue. The resulting candidate splice variants were validated with RT-PCR. We found nine genes that were differentially spliced between colon tumors and normal colon tissues, several of which have not been previously implicated in cancer. Top scoring candidates from our analysis were also found to substantially overlap with EST-based bioinformatic predictions of alternative splicing in cancer.

Conclusion

Differential expression of high confidence transcripts correlated extremely well with known cancer genes and pathways, suggesting that the more speculative transcripts, largely based solely on computational prediction and mostly with no previous annotation, might be novel targets in colon cancer. Five of the identified splicing events affect mediators of cytoskeletal organization (ACTN1, VCL, CALD1, CTTN, TPM1), two affect extracellular matrix proteins (FN1, COL6A3) and another participates in integrin signaling (SLC3A2). Altogether they form a pattern of colon-cancer specific alterations that may particularly impact cell motility.
Generation and characterization of a stable cell population releasing fluorescent HIV-1-based Virus Like Particles in an inducible way
Authors: Muratori Claudia , D'Aloja Paola , Superti Fabiana , Tinari Antonella , Sol-Foulon Nathalie , Sparacio Sandra , Bosch Valerie , Schwartz Olivier , Federico Maurizio
Published: December 2006

Background

The availability of cell lines releasing fluorescent viral particles can significantly support a variety of investigations, including the study of virus-cell interaction and the screening of antiviral compounds. Regarding HIV-1, the recovery of such biologic reagents represents a very hard challenge due to the intrinsic cytotoxicity of many HIV-1 products. We sought to overcome such a limitation by using a cell line releasing HIV-1 particles in an inducible way, and by exploiting the ability of a HIV-1 Nef mutant to be incorporated in virions at quite high levels.

Results

Here, we report the isolation and characterization of a HIV-1 packaging cell line, termed 18-4s, able to release valuable amounts of fluorescent HIV-1 based Virus-Like Particles (VLPs) in an inducible way. 18-4s cells were recovered by constitutively expressing the HIV-1 NefG3C mutant fused with the enhanced-green fluorescent protein (NefG3C-GFP) in a previously isolated inducible HIV-1 packaging cell line. The G3C mutation creates a palmitoylation site which results in NefG3C-GFP incorporation into virions greatly exceeding that of the wild type counterpart. Upon induction of 18-4s cells with ponasterone A and sodium butyrate, up to 4 μg/ml of VLPs, which had incorporated about 150 molecules of NefG3C-GFP per viral particle, were released into the culture supernatant. Due to their intrinsic strong fluorescence, the 18-4s VLPs were easily detectable by a novel cytofluorometric-based assay developed here. The treatment of target cells with fluorescent 18-4 VLPs pseudotyped with different glycoprotein receptors resulted in these becoming fluorescent as early as two hours post-challenge.

Conclusion

We created a stable cell line releasing fluorescent HIV-1 based VLPs upon induction useful for several applications including the study of virus-cell interactions and the screening of antiviral compounds.
Liver metastases of pancreatic acinar cell carcinoma with marked nuclear atypia and pleomorphism diagnosed by EUS FNA cytology : A case report with emphasis on FNA cytological findings
Authors: Peng Hong Q , Darwin Peter , Papadimitriou John C , Drachenberg Cinthia B
Published: December 2006

Background:

Acinar cell carcinoma of the pancreas is a rare neoplasm. Although this tumor has been well characterized histologically, the morphological patterns in Fine Needle Aspiration Cytology have not been well defined. Unlike ductal adenocarcinomas, endocrine tumors, and solid pseudopapillary tumors of the pancreas with their characteristic FNA cytological features, acinar cell carcinomas pose a particular diagnostic challenge by sharing many cytomorphologic features with endocrine tumors of the pancreas.

Case presentation:

A 37-year-old man presented with lower chest and left upper quadrant abdominal pain. Computed tomography revealed a 7.8 x 7.3 cm irregular, partially cystic mass in the body and tail of the pancreas, and two lesions in the liver compatible with metastases. Subsequently, the patient underwent endoscopic ultrasound-guided fine needle aspiration on one of the two metastatic liver masses.

Conclusion:

We describe a case of pancreatic acinar cell carcinoma with unusual cytomorphologic features mimicking an endocrine tumor of pancreas, encountered in endoscopic ultrasound-guided fine needle aspiration of a metastatic liver mass and discuss the diagnostic approach for this unusual pancreatic tumor in fine needle aspiration cytology.
Role of histamine as a putative inhibitory transmitter in the honeybee antennal lobe
Authors: Sachse Silke , Peele Philipp , Silbering Ana F , Gühmann Martin , Galizia C Giovanni
Published: December 2006

Background

Odors are represented by specific spatio-temporal activity patterns in the olfactory bulb of vertebrates and its insect analogue, the antennal lobe. In honeybees inhibitory circuits in the AL are involved in the processing of odors to shape afferent odor responses. GABA is known as an inhibitory transmitter in the antennal lobe, but not all interneurons are GABAergic. Therefore we sought to analyze the functional role of the inhibitory transmitter histamine for the processing of odors in the honeybee AL.

Results

We optically recorded the representation of odors before, during and after histamine application at the input level (estimated from a compound signal), and at the output level (by selectively measuring the projection neurons). For both, histamine led to a strong and reversible reduction of odor-evoked responses.

Conclusion

We propose that histamine, in addition to GABA, acts as an inhibitory transmitter in the honeybee AL and is therefore likely to play a role in odor processing.
Recent Advances in Basic Neurosciences and Brain Disease: From Synapses to Behavior
Authors: Bi Guo-Qiang , Bolshakov Vadim , Bu Guojun , Cahill Catherine M , Chen Zhou-Feng , Collingridge Graham L , Cooper Robin L , Coorssen Jens R , El-Husseini Alaa , Galhardo Vasco , Gan Wen-Biao , Gu Jianguo , Inoue Kazuhide , Isaac John , Iwata Koichi , Jia Zhengping , Kaang Bong-Kiun , Kawamata Mikito , Kida Satoshi , Klann Eric , Kohno Tatsuro , Li Min , Li Xiao-Jiang , MacDonald John F , Nader Karim , Nguyen Peter V , Oh Uhtaek , Ren Ke , Roder John C , Salter Michael W , Song Weihong , Sugita Shuzo , Tang Shao-Jun , Tao Yuanxiang , Wang Yu Tian , Woo Newton , Woodin Melanie A , Yan Zhen , Yoshimura Megumu , Xu Ming , Xu Zao C , Zhang Xia , Zhen Mei , Zhuo Min
Published: December 2006

Understanding basic neuronal mechanisms hold the hope for future treatment of brain disease. The 1st international conference on synapse, memory, drug addiction and pain was held in beautiful downtown Toronto, Canada on August 21–23, 2006. Unlike other traditional conferences, this new meeting focused on three major aims: (1) to promote new and cutting edge research in neuroscience; (2) to encourage international information exchange and scientific collaborations; and (3) to provide a platform for active scientists to discuss new findings. Up to 64 investigators presented their recent discoveries, from basic synaptic mechanisms to genes related to human brain disease. This meeting was in part sponsored by Molecular Pain, together with University of Toronto (Faculty of Medicine, Department of Physiology as well as Center for the Study of Pain). Our goal for this meeting is to promote future active scientific collaborations and improve human health through fundamental basic neuroscience researches. The second international meeting on Neurons and Brain Disease will be held in Toronto (August 29–31, 2007).
Quality of life and salivary output in patients with head-and-neck cancer five years after radiotherapy
Authors: Braam Pètra M , Roesink Judith M , Raaijmakers Cornelis PJ , Busschers Wim B , Terhaard Chris HJ
Published: January 2007

Background

To describe long-term changes in time of quality of life (QOL) and the relation with parotid salivary output in patients with head-and-neck cancer treated with radiotherapy.

Methods

Forty-four patients completed the EORTC-QLQ-C30(+3) and the EORTC-QLQ-H&N35 questionnaires before treatment, 6 weeks, 6 months, 12 months, and at least 3.5 years after treatment. At the same time points, stimulated bilateral parotid flow rates were measured.

Results

There was a deterioration of most QOL items after radiotherapy compared with baseline, with gradual improvement during 5 years follow-up. The specific xerostomia-related items showed improvement in time, but did not return to baseline. Global QOL did not alter significantly in time, although 41% of patients complained of moderate or severe xerostomia at 5 years follow-up. Five years after radiotherapy the mean cumulated parotid flow ratio returned to baseline but 20% of patients had a flow ratio <25%. The change in time of xerostomia was significantly related with the change in flow ratio (p = 0.01).

Conclusion

Most of the xerostomia-related QOL scores improved in time after radiotherapy without altering the global QOL, which remained high. The recovery of the dry mouth feeling was significantly correlated with the recovery in parotid flow ratio.
Routine versus Selective Abdominal Computed Tomography Scan in the Evaluation of Right Lower Quadrant Pain: A Randomized Controlled Trial
Authors: Lee Christopher C. , Golub Robert , Singer Adam J. , Cantu Roberto , Levinson Howard
Published: December 2006

Objectives

To determine the role of abdominal computed tomography (CT) imaging in patients with right lower quadrant (RLQ) pain. The authors hypothesized that selective use of abdominal CT would reduce imaging without increasing the rates of negative appendectomy and perforated appendicitis.

Methods

A prospective randomized clinical trial was conducted in a community teaching emergency department. Adult patients with acute RLQ abdominal pain with suspected acute appendicitis were included. Patients were randomized to mandatory (all patients) or selective (based on clinical evaluation) abdominal CT imaging. The primary outcome was the negative appendectomy rate.

Results

A total of 152 patients were randomized to selective (n= 80) and mandatory (n= 72) intervention groups. The mean (±SD) age was 34.1 (±3.5) years, and 48% were female. CT imaging was performed in 54 of 80 patients (68%; 95% confidence interval [CI] = 56% to 78%) in the selective group and in 70 of 72 patients (97%; 95% CI = 90% to 100%) in the mandatory group. There was a trend to a decreased rate of negative appendectomy in the mandatory group (1/39 [2.6%]; 95% CI = 0.5% to 13.2%) as compared with the selective group (6/43 [13.9%]; 95% CI = 6.6% to 27.3%), with a difference in prevalence rates of 11.3% (95% CI =−3.5% to 26.3%). There was also a trend to a decreased perforated appendix rate in the mandatory group (4/39 [10.3%]) as compared with the selective group (7/38 [18.4%]), with a difference in prevalence rates of 8.2% (95% CI =−8.0% to 24.4%).

Conclusions

In this small sample of adult patients with RLQ abdominal pain and suspected acute appendicitis, CT imaging was performed less frequently in the selective group and there was a trend with mandatory CT imaging to reduced rates of negative appendectomy and perforated appendices.