bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outer Membrane Vesicle Production by
Escherichia coli
Is Independent of Membrane Instability
Authors: McBroom Amanda J. , Johnson Alexandra P. , Vemulapalli Sreekanth , Kuehn Meta J. 
Published: July 2006

ABSTRACT

It has been long noted that gram-negative bacteria produce outer membrane vesicles, and recent data demonstrate that vesicles released by pathogenic strains can transmit virulence factors to host cells. However, the mechanism of vesicle release has remained undetermined. This genetic study addresses whether these structures are merely a result of membrane instability or are formed by a more directed process. To elucidate the regulatory mechanisms and physiological basis of vesiculation, we conducted a screen in
Escherichia coli
to identify gene disruptions that caused vesicle over- or underproduction. Only a few low-vesiculation mutants and no null mutants were recovered, suggesting that vesiculation may be a fundamental characteristic of gram-negative bacterial growth. Gene disruptions were identified that caused differences in vesicle production ranging from a 5-fold decrease to a 200-fold increase relative to wild-type levels. These disruptions included loci governing outer membrane components and peptidoglycan synthesis as well as the σ
E
cell envelope stress response. Mutations causing vesicle overproduction did not result in upregulation of the
ompC
gene encoding a major outer membrane protein. Detergent sensitivity, leakiness, and growth characteristics of the novel vesiculation mutant strains did not correlate with vesiculation levels, demonstrating that vesicle production is not predictive of envelope instability.
Addiction Toxin Fst Has Unique Effects on Chromosome Segregation and Cell Division inEnterococcus faecalisandBacillussubtilis
Authors: Patel S. , Weaver K. E. 
Published: July 2006

ABSTRACTThe Fst toxin of theEnterococcus faecalispAD1-encodedparaddiction module functions intracellularly to kill plasmid-free segregants. Previous results had shown that Fst induction results in membrane permeabilization and cessation of macromolecular synthesis, but only after 45 min. Electron micrographs of toxin-induced cells showed no obvious membrane abnormalities but did reveal defects in nucleoid segregation and cell division, begging the question of which is the primary effect of Fst. To distinguish the possibilities, division septae and nucleoids were visualized simultaneously with fluorescent vancomycin and a variety of DNA stains. Results showed that division and segregation defects occurred in some cells within 15 min after induction. At these early time points, affected cells remained resistant to membrane-impermeant DNA stains, suggesting that loss of membrane integrity is a secondary effect caused by ongoing division and/or segregation defects. Fst-resistant mutants showed greater variability in cell length and formed multiple septal rings even in the absence of Fst. Fst induction was also toxic toBacillus subtilis. In this species, Fst induction caused only minor division abnormalities, but all cells showed a condensation of the nucleoid, suggesting that effects on the structure of the chromosomal DNA might be paramount.
Warfarin-related outcomes in patients with antiphospholipid antibody syndrome managed in an anticoagulation clinic
Authors: Downing Jennifer , Blackburn Juan , Nutescu Edith , Wittkowsky Ann 
Published: July 2006

SummaryPatients with antiphospholipid antibody syndrome (APA) are at elevated risk of venous and arterial thromboembolic complications. Oral anticoagulation with warfarin is recommended for secondary prevention of thromboembolism, but warfarin-related outcomes have not been systematically investigated when warfarin therapy is managed by a dedicated anticoagulation clinic.The objectives of the study were to evaluate warfarin-related monitoring outcomes, clinical endpoints and the use of healthcare resources as a result of warfarin-related complications in patients with APA compared to a group of patients without APA, all of whom were managed in an anticoagulation clinic setting. A retrospective observational cohort design was used to investigate patients with and without APA, all of whom had a history of venous or arterial thromboembolism, and were matched for age, gender and indication for oral anticoagulation. Thirty-six APA patients taking warfarin were compared to a matched cohort of 36 patients without APA. Monitoring outcomes (time in therapeutic range, clinic visits per year, frequency of warfarin dosing adjustments, reasons for out-of-range INRs) were similar between groups, as was the frequency of major bleeding complications (3.2%/pt-yr vs. 3.1%/pt-yr). However, recurrent thromboembolic events (9.6%/pt-yr vs 0) occurred more frequently in APA patients. APA patients required more emergency room visits (6.4%/pt-yr vs. 1.6%/pt-yr) and hospital admissions (14.4%/pt-yr vs.3.0%/pt-yr) to manage complications of warfarin therapy. In conclusion, despite similar monitoring outcomes obtained in a dedicated anticoagulation clinic setting, adverse clinical outcomes are significantly more frequent in patients with APA syndrome than in those without APA, and require more frequent use of healthcare resources.
Ovarian vein thrombosis: Incidence of recurrent venous thromboembolism and survival
Authors: Wysokinska Ewa , Hodge David , McBane Robert 
Published: July 2006

SummaryFor patients with ovarian vein thrombosis (OVT), neither the rate of recurrence nor the expected survival are well established. Clarification of these natural history data would aid in defining the optimal management. We studied all female patients with OVT seen at the Mayo Clinic between 1990 and 2006. Survival, recurrent venous thrombosis rates, and prothrombotic factors were compared to a randomly selected group of 114 female patients with lower extremity venous thrombosis (DVT). Patients with OVT (n=35; mean age 44.8 ± 17.9 years) were significantly more likely to be under hormonal stimulation (48%), have an underlying malignancy (34%), experienced recent pelvic infection (23%) or undergone recent surgery (20%), compared to DVT patients. Duringa mean follow-up period of 34.6 ± 44.3 months, three patients suffered three recurrent venous thrombi (event rate: three per 100 patient years of follow-up).This recurrence rate was comparable to patients with lower extremity DVT (2.2 per 100 patient years). Recurrent thrombosis involved the contralateral ovarian vein, left renal vein, and inferior vena cava. The five-year mortality rate for OVT patients was 43% compared to 20% for DVT patients (p=0.08). All OVT deaths were cancer related. Survival was greater in OVT patients without cancer compared to those with active cancer (p<0.0001). In conclusion, venous thromboembolism recurrence rates are low and comparable to lower extremity DVT. Therefore general treatment guidelines for lower extremity DVT may be applicable. Poor survival rates in OVT are principally governed by the presence of malignancy.
Incidence of arterial cardiovascular events in patients with idiopathic venous thromboembolism
Authors: Marchiori Antonio , Noto Alfonso , Rossi Vincenza , Daniele Filomena , Santoro Caterina , Ricchio Roberto , De Lorenzo Roberto , Umbaca Rossella , Prandoni Paolo , Bova Carlo 
Published: July 2006

SummaryRecent data have showna higher incidence of arterial events in patients with venous thromboembolism (VTE) of unknown origin than in those with the secondary form of disease. Whether patients with idiopathic VTE have a higher risk of subsequent arterial events than the general population is unknown. The aim was to evaluate the rates of subsequent arterial events in patients with idiopathic VTE and control subjects. In a retrospective cohort study we compared the rates of subsequent arterial events (i.e. acute myocardial infarction, ischemic stroke and peripheral arterial disease) in 151 consecutive patients with objectively confirmed spontaneousVTE and 151 control subjects randomly selected from the database of two family physicians. We collected information about cardiovascular risk-factors (hypertension, hypercholesterolemia, diabetes, obesity and smoke) at the time of VTE episode, or corresponding date for the controls, and considered the follow-up from this time. Patients and controls who had suffered from arterial events before the index date were excluded. During a mean follow-up of 43.1 (± 21.7) months there were 16 arterial events in theVTE patients and six in the control group (HR, 2.84; 95% CI, 1.11 to 7.27; p= 0.03).The difference remained significant after adjusting for age and other cardiovascular risk factors (HR 2.86; 95% CI, 1.07 to 7.62).Overall mortality was also higher in theVTE patients (12 vs.4 deaths). In conclusion, arterial events are more common in patients with previous idiopathic VTE than in the general population. These findings may have practical implications.
Ex vivo evaluation of anti-GPVI antibody in Cynomolgus monkeys: Dissociation between anti-platelet aggregatory effect and bleeding time
Authors: Matsumoto Yutaka , Takizawa Hisao , Nakama Kazuhiro , Gong Xiaoqi , Yamada Yoshihisa , Tandon Narendra , Kambayashi Junichi 
Published: July 2006

SummaryRecent progress in the understanding of thrombus formation has suggested an important role of glycoprotein (GP)VI. In contrast to its pivotal role in collagen-induced platelet activation, it has been suggested that its blockade does not induce massive bleeding tendency. To demonstrate the dissociation between inhibitory effect on platelet aggregation and bleeding by GPVI blockade, we examined the effects of Fab fragment of OM2, an anti-human GPVI monoclonal antibody on ex vivo collagen-induced platelet aggregation and skin bleeding time after intravenous injection in cynomolgus monkeys. In a dose-escalation study, OM2 potently (>80%) inhibited collagen-induced platelet aggregation at the cumulative dose of 0. 2 mg/kg with a slight prolongation of bleeding time (1. 3 times baseline value). Furthermore, at 18. 8 mg/kg, the highest dose tested, prolongation of bleeding time was still mild (1. 9 times). In contrast, abciximab, Fab fragment of anti-GPIIb/IIIa antibody prolonged bleeding time by 5. 0 times at 0. 35 mg/kg, the lowest effective dose on platelet aggregation. Ina pharmacodynamic study,a bolus injection of OM2 at 0. 4 mg/kg produced potent inhibition of collagen-induced aggregation up to six hours after injection, showing longer half-life than that of abciximab. The injection of OM2 Fab did not induce thrombocytopenia and GPVI depletion in monkeys. These results suggest that blockade of GPVI by antibody can exerta potent inhibitory effect on collagen-induced platelet aggregation with a milder prolongation of bleeding time than blockade of GPIIb/IIIa. This study indicates that OM2 has the potential to be developed as a new class of therapeutic tool.
African Proverbs as a Medium of Fostering Intergenerational Relationships and Communication in the Niger Delta, Nigeria
Authors: Oduaran Akpovire , Oduaran Choja 
Published: July 2006

AbstractThis brief paper examines, from the point of view of ethnography, how the African proverbs selected from the Niger Delta of Nigeria have been used in fostering intergenerational relationships discourse in a globalizing world. This discussion adopts the ethnographic approach in exploring the meaning and functions aims, structures and the delivery modes of African proverbs used in intergenerational relationships as our peoples struggle with the threat to the erosion of some of the major positive artefacts in our culture. It concludes by synthesizing contemporary challenges seemingly minimizing the overall use and impacts of African proverbs in intergenerational relationships, and suggesting the possible implications of the discussion for networking regionally and globally.
The Rhetoric of Unity and the Quest for Political Power in Nigeria
Authors: Alumona Victor 
Published: July 2006

AbstractPost colonial African countries, like Nigeria, have been contending, in one form or another, with the problems of nation building. One of these problems in the post independent era is that of forging one nation from a plethora of peoples and cultures brought together under one flag by the erstwhile colonialists. The author argues that even though the various Nigerian political elite usually give the impression that National unity is a sine qua non for the existence of Nigeria as a state and a country, and that every one who must be considered a patriot must be seen to be rooting for it, the real thing, however, is that they emphasize national unity as a leverage for political power. In other words, they see in Unity of the country a topic for generating arguments to support their drive for political power, or to justify their retention of it in spite of the means used to achieve these ends.A careful consideration of the policies of these elite while in government show that they use Unity of Nigeria expediently like the rhetoricians of ancient Greece would do, not out of principles but to serve a contingent purpose. The unity of Nigeria became a source of arguments for power ever before independence because the Northern region feared domination by the Southern region given its many advantages.
China's New Mercantilism in Central Africa
Authors: Holslag Jonathan 
Published: July 2006

AbstractThe objective of this article is twofold. On one hand it elucidates the goals and dynamics of China's foreign trade policy since the 1990s. On the other hand it assesses the impact of this strategy on the development of the Central African Region as a case for China's influence on other developing countries. We observe that China is pursuing a pragmatic mercantilist policy that combines a wide array of diplomatic and economic devices. As a result the People's Republic gains ground slowly but surely. However, China's ascent does not lift the Central African states to a more favourable position in the global division of labour. We conclude that China's rise confirms the current economic position of African countries: that of a commodity supplier and a modest consumer's market.
The growing momentum and legitimacy behind an alliance for international education
Authors: Bunnell Tristan 
Published: July 2006

English Within the diverse universe of internationally minded schools there is currently much momentum behind the creation of some form of ‘alliance’. Although the movement behind this can be traced back to the early 1990s, this article proposes that the current momentum can be largely understood within a fundamental paradigm shift emerging within education generally, towards greater collaboration, networking and partnership. This arguably gives the ‘alliance’ project a much greater deal of legitimacy than has previously been implied. At the same time, a further set of complex factors can be identified within the universe of internationally minded schools. French Il existe actuellement une grande aspiration en vue de créer une certaine forme 'd'alliance' au sein de la diversité d'établissements scolaires sensibles à la réalité internationale. Bien que ce mouvement remonte au début des añes 90, cet article suggère que l'impulsion actuelle s'inscrit en grande partie dans le cadre d'une mutation profonde qui voit le jour dans l'éducation en général, en vue de renforcer les collaborations et de développer les réseaux de contacts et les partenariats. Ainsi, ce projet 'd'alliance' a sans doute une plus grande légitimité aujourd'hui qu'on ne le supposait auparavant. Parallèlement, l'article permet d'identifier un ensemble supplémentaire de facteurs complexes au sein des établissements scolaires sensibles à la réalité internationale. Spanish En estos momentos, en el universo variopinto de los colegios con orientación internacional, se hace mucho hincapié en crear algún tipo de 'alianza'. Aunque esta tendencia se puede remontar a principios de los años 90, en este estudio se sugiere que se puede comprender esta tendencia en el marco de un cambio de paradigma fundamental que empieza a surgir en el sector de la educación en general. Este cambio consiste en buscar más colaboraciones, redes de contacto y asociaciones, y le da al proyecto de 'alianzas' un grado de legitimidad mayor que el que ten'a anteriormente. Además, dentro del universo de los colegios con orientación internacional, puede identificarse también otro grupo de factores complejos.
The international school industry
Authors: MacDonald James 
Published: July 2006

English Based upon the results of a quantitative analysis of tuition revenues generated by international schools, it is argued that international schools can be examined in terms of a global multi-billion dollar industry and that business theory can be, and is being, applied in international schools today. This article proposes that international schools are organizations with double bottom lines - one educational and one business - and suggests that only by peering through a set of properly aligned educational and business lenses can a true and clear picture of an international school be obtained. French D'après les résultats d'une analyse quantitative sur les revenus générés par les frais de scolarité des établissements scolaires internationaux, il apparaîtrait que ces derniers représentent une industrie mondiale se chiffrant en milliers de milliards de dollars américains. En outre, cette théorie commerciale peut s'appliquer, et est même appliquée, dans les établissements scolaires internationaux de nos jours. Cet article suggère que les établissements scolaires internationaux constituent des organisations ayant une double activité; l'une éducative, l'autre commerciale. Il avance également que ce n'est qu'en trouvant un équilibre entre ces deux perspectives que l'on peut avoir une idée précise de ce que représente un établissement scolaire international. Spanish Basándose en los resultados de un análisis cuantitativo de los ingresos que generan las tasas de matriculación en los colegios internacionales, este artículo argumenta que los colegios internacionales pueden considerarse una industria mundial valorada en miles de millones de dólares a la que actualmente puede aplicarse, y de hecho se aplica, la teoría empresarial. Sugiere que los colegios internacionales son organizaciones con dos ejes principales, uno educativo y otro empresarial, y que sólo puede obtenerse una impresión clara y realista de un colegio internacional si se analiza desde una perspectiva educativa y una perspectiva empresarial debidamente alineadas.
The CML-related oncoprotein BCR/ABL induces expression of histidine decarboxylase (HDC) and the synthesis of histamine in leukemic cells
Authors: Aichberger Karl J. , Mayerhofer Matthias , Vales Anja , Krauth Maria-Theresa , Gleixner Karoline V. , Bilban Martin , Esterbauer Harald , Sonneck Karoline , Florian Stefan , Derdak Sophia , Pickl Winfried F. , Agis Hermine , Falus Andras , Sillaber Christian , Valent Peter 
Published: July 2006

AbstractBasophil numbers are typically elevated in chronic myeloid leukemia (CML) and increase during disease progression. Histamine is an essential mediator and marker of basophils and is highly up-regulated in CML. We examined the biochemical basis of histamine synthesis in CML cells. The CML-specific oncoprotein BCR/ABL was found to promote expression of histidine decarboxylase (HDC) and synthesis of histamine in Ba/F3 cells. Moreover, the BCR/ABL tyrosine kinase inhibitors imatinib (STI571) and nilotinib (AMN107) decreased histamine levels and HDC mRNA expression in BCR/ABL-transformed Ba/F3 cells, in the CML-derived basophil cell line KU812, and in primary CML cells. Synthesis of histamine was found to be restricted to the basophil compartment of the CML clone and to depend on signaling through the PI3-kinase pathway. CML cells also expressed histamine receptors (HRs), including HR-1, HR-2, HR-4, and histamine-binding CYP450 isoenzymes which also serve as targets of HR antagonists. The HR-1 antagonists loratadine and terfenadine, which bind to CYP450, were found to counteract proliferation of CML cells, whereas no growth inhibition was observed with the HR-1 antagonist fexofenadine which is not targeted or metabolized by CYP450. Moreover, DPPE, an inhibitor of histamine-binding CYP450 isoenzymes, produced growth inhibition in CML cells. Together, these data show that BCR/ABL promotes histamine production in CML cells and that certain HR-targeting drugs exert antileukemic effects on CML cells.
MicroRNAs modulate the angiogenic properties of HUVECs
Authors: Poliseno Laura , Tuccoli Andrea , Mariani Laura , Evangelista Monica , Citti Lorenzo , Woods Keith , Mercatanti Alberto , Hammond Scott , Rainaldi Giuseppe 
Published: July 2006

AbstractMicroRNAs (miRNAs) have recently come into focus as key posttranscriptional modulators of gene expression. In this work, we addressed whether in vitro angiogenesis is an miRNA-regulated process. We performed large-scale analysis of miRNA expression in human umbilical vein endothelial cells (HUVECs) and found that 15 highly expressed miRNAs have the receptors of angiogenic factors as putative targets. In particular, we demonstrated that miR-221 and miR-222 affect c-Kit expression and, as a consequence, the angiogenic properties of its ligand stem cell factor. Interaction between miR-222 and c-Kit is likely to be part of a complex circuit that controls the ability of endothelial cells to form new capillaries.
MIP-1α (CCL3) is a downstream target of FGFR3 and RAS-MAPK signaling in multiple myeloma
Authors: Masih-Khan Esther , Trudel Suzanne , Heise Carla , Li Zhihua , Paterson Joshua , Nadeem Vincent , Wei Ellen , Roodman David , Claudio Jaime O. , Bergsagel P. Leif , Stewart A. Keith 
Published: July 2006

Abstract
Overexpression of fibroblast growth factor receptor 3 (FGFR3) is a hallmark of t(4;14) multiple myeloma (MM). To dissect the mechanism of FGFR3 oncogenesis in MM, we used 3 FGFR selective kinase inhibitors—CHIR258, PD173074, and SU5402—and FGFR3-specific siRNA to modulate FGFR3 activity. Conversely, the ligand FGF was used to stimulate FGFR3 function in human MM cells. The transcriptional response to FGFR3 modification was recorded, and gene expression changes common to all 5 modifiers were documented. Ten genes were commonly regulated. Macrophage inflammatory protein-1 alpha (MIP-1α) was the single most differentially altered gene. MIP-1 α promoter function, gene expression, and protein secretion were each down-regulated following inhibition of FGFR3 signaling. Down-regulation of MIP-1 α was not, however, observed following FGFR3 inhibition in MM cells with RAS mutations implicating RAS-MAPK in MIP-1 α regulation. As confirmation, inhibition of ERK1 also down-regulated MIP-1 α in FGFR3 inhibitor-resistant cells harboring RAS mutations. MIP-1 α is implicated in the survival and proliferation of MM cells and the pathogenesis of MM bone disease. Our observation is the first to directly link an initiating IgH translocation not only to MM-cell growth and survival but also to the disease-associated bone disease.