bluuebunny/crossref_metadata_2025 huggingface dataset:
Angiopoietin-2 predicts disease-free survival after allogeneic stem cell transplantation in patients with high-risk myeloid malignancies
Authors: Kümpers Philipp , Koenecke Christian , Hecker Hartmut , Hellpap Julian , Horn Rüdiger , Verhagen Willem , Buchholz Stefanie , Hertenstein Bernd , Krauter Jürgen , Eder Matthias , David Sascha , Göhring Gudrun , Haller Hermann , Ganser Arnold
Published: May 2008

Emerging data suggest a critical role for bone marrow angiogenesis in hematologic malignancies. The angiopoietin/Tie ligand-receptor system is an essential regulator of this process. We evaluated whether circulating angiopoietin-2 (Ang-2) is a predictor for the probability of disease-free survival (DFS) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) for high-risk acute myeloid leukemia or myelodysplastic syndrome. Ang-2 was measured by enzyme-linked immunosorbent assay in serum from 20 healthy controls and 90 patients with acute myeloid leukemia or myelodysplastic syndrome before conditioning for HSCT. Circulating Ang-2 was elevated in patients (median, 2.21 ng/mL; range, 0.18-48.84 ng/mL) compared with controls (median, 0.87 ng/mL; range, 0.27-4.51 ng/mL; P < .001). Multivariate analyses confirmed the independent prognostic impact of Ang-2 (hazard ratio [HR] = 2.46; 95% confidence interval [CI], 1.27-4.76, P = .005), percentage of bone marrow infiltration (HR = 1.14; 95% CI, 1.01-1.29, P = .033), and chemotherapy cycles before HSCT (HR = 1.38; 95% CI, 1.01-1.08, P = .048). Regression tree analysis detected optimal cutoff values for Ang-2 and recursively identified bone marrow blasts and Ang-2 as the best predictors for DFS. Because few predictors for DFS exist in the setting of allo-HSCT, Ang-2 may be used as a readily available powerful biomarker to pre-estimate DFS and may open new perspectives for risk-adapted treatment of high-risk myeloid malignancies.
YRRL motifs in the cytoplasmic domain of the thrombopoietin receptor regulate receptor internalization and degradation
Authors: Hitchcock Ian S. , Chen Maximus M. , King Jennifer R. , Kaushansky Kenneth
Published: May 2008

Thrombopoietin (Tpo), acting through the c-Mpl receptor, promotes the survival and proliferation of hematopoietic stem and progenitor cells and drives megakaryocyte differentiation. The proproliferation and survival signals activated by Tpo must therefore be tightly regulated to prevent uncontrolled cell growth. In this work, we determined the mechanisms that control Tpo-stimulated c-Mpl internalization and defined the processes leading to its degradation. Stimulation of BaF-Mpl cells with Tpo leads to rapid, clathrin-dependent endocytosis of the receptor. Using small interfering RNA (siRNA), we found that inhibition of adaptor protein 2 (AP2), which mediates endocytosis of transmembrane proteins, strongly attenuates Tpo-stimulated c-Mpl internalization. AP2 interacts with YXXΦ motifs and we identified 2 such motifs in c-Mpl (Y8RRL and Y78RRL) and investigated Tpo-stimulated internalization of receptors bearing point mutations at these sites. After Tpo stimulation, internalization was greatly reduced in c-Mpl Y78F and c-Mpl Y8+78F, and these cell lines also exhibited increased proliferation and increased strength and duration of Jak2, STAT5, AKT, and ERK1/2 activation in response to Tpo. We also found that the Y8RRL motif regulates Tpo-stimulated lysosomal degradation of c-Mpl. Our data establishes that c-Mpl cytoplasmic YRRL motifs are responsible for both Tpo-mediated internalization via interactions with AP2 and lysosomal targeting after endocytosis.
Unraveling the evolutionary history of the phosphoryl-transfer chain of the phosphoenolpyruvate:phosphotransferase system through phylogenetic analyses and genome context
Authors: Comas Iñaki , González-Candelas Fernando , Zúñiga Manuel
Published: May 2008

Background

The phosphoenolpyruvate phosphotransferase system (PTS) plays a major role in sugar transport and in the regulation of essential physiological processes in many bacteria. The PTS couples solute transport to its phosphorylation at the expense of phosphoenolpyruvate (PEP) and it consists of general cytoplasmic phosphoryl transfer proteins and specific enzyme II complexes which catalyze the uptake and phosphorylation of solutes. Previous studies have suggested that the evolution of the constituents of the enzyme II complexes has been driven largely by horizontal gene transfer whereas vertical inheritance has been prevalent in the general phosphoryl transfer proteins in some bacterial groups. The aim of this work is to test this hypothesis by studying the evolution of the phosphoryl transfer proteins of the PTS.

Results

We have analyzed the evolutionary history of the PTS phosphoryl transfer chain (PTS-ptc) components in 222 complete genomes by combining phylogenetic methods and analysis of genomic context. Phylogenetic analyses alone were not conclusive for the deepest nodes but when complemented with analyses of genomic context and functional information, the main evolutionary trends of this system could be depicted.

Conclusion

The PTS-ptc evolved in bacteria after the divergence of early lineages such as Aquificales, Thermotogales and Thermus/Deinococcus. The subsequent evolutionary history of the PTS-ptc varied in different bacterial lineages: vertical inheritance and lineage-specific gene losses mainly explain the current situation in Actinobacteria and Firmicutes whereas horizontal gene transfer (HGT) also played a major role in Proteobacteria. Most remarkably, we have identified a HGT event from Firmicutes or Fusobacteria to the last common ancestor of the Enterobacteriaceae, Pasteurellaceae, Shewanellaceae and Vibrionaceae. This transfer led to extensive changes in the metabolic and regulatory networks of these bacteria including the development of a novel carbon catabolite repression system. Hence, this example illustrates that HGT can drive major physiological modifications in bacteria.
The complete mitochondrial genomes for three Toxocara species of human and animal health significance
Authors: Li Ming-Wei , Lin Rui-Qing , Song Hui-Qun , Wu Xiang-Yun , Zhu Xing-Quan
Published: May 2008

Background

Studying mitochondrial (mt) genomics has important implications for various fundamental areas, including mt biochemistry, physiology and molecular biology. In addition, mt genome sequences have provided useful markers for investigating population genetic structures, systematics and phylogenetics of organisms. Toxocara canis, Toxocara cati and Toxocara malaysiensis cause significant health problems in animals and humans. Although they are of importance in human and animal health, no information on the mt genomes for any of Toxocara species is available.

Results

The sizes of the entire mt genome are 14,322 bp for T. canis, 14029 bp for T. cati and 14266 bp for T. malaysiensis, respectively. These circular genomes are amongst the largest reported to date for all secernentean nematodes. Their relatively large sizes relate mainly to an increased length in the AT-rich region. The mt genomes of the three Toxocara species all encode 12 proteins, two ribosomal RNAs and 22 transfer RNA genes, but lack the ATP synthetase subunit 8 gene, which is consistent with all other species of Nematode studied to date, with the exception of Trichinella spiralis. All genes are transcribed in the same direction and have a nucleotide composition high in A and T, but low in G and C. The contents of A+T of the complete genomes are 68.57% for T. canis, 69.95% for T. cati and 68.86% for T. malaysiensis, among which the A+T for T. canis is the lowest among all nematodes studied to date. The AT bias had a significant effect on both the codon usage pattern and amino acid composition of proteins. The mt genome structures for three Toxocara species, including genes and non-coding regions, are in the same order as for Ascaris suum and Anisakis simplex, but differ from Ancylostoma duodenale, Necator americanus and Caenorhabditis elegans only in the location of the AT-rich region, whereas there are substantial differences when compared with Onchocerca volvulus,Dirofiliria immitis and Strongyloides stercoralis. Phylogenetic analyses based on concatenated amino acid sequences of 12 protein-coding genes revealed that the newly described species T. malaysiensis was more closely related to T. cati than to T. canis, consistent with results of a previous study using sequences of nuclear internal transcribed spacers as genetic markers.

Conclusion

The present study determined the complete mt genome sequences for three roundworms of human and animal health significance, which provides mtDNA evidence for the validity of T. malaysiensis and also provides a foundation for studying the systematics, population genetics and ecology of these and other nematodes of socio-economic importance.
Constitutive Expressor of Pathogenesis-Related Genes5affects cell wall biogenesis and trichome development
Authors: Brininstool Ginger , Kasili Remmy , Simmons L Alice , Kirik Viktor , Hülskamp Martin , Larkin John C
Published: May 2008

Background

The Arabidopsis thaliana CONSTITUTIVE EXPRESSOR OF PATHOGENESIS-RELATED GENES5 (CPR5) gene has been previously implicated in disease resistance, cell proliferation, cell death, and sugar sensing, and encodes a putative membrane protein of unknown biochemical function. Trichome development is also affected in cpr5 plants, which have leaf trichomes that are reduced in size and branch number.

Results

In the work presented here, the role of CPR5 in trichome development was examined. Trichomes on cpr5 mutants had reduced birefringence, suggesting a difference in cell wall structure between cpr5 and wild-type trichomes. Consistent with this, leaf cell walls of cpr5 plants contained significantly less paracrystalline cellulose and had an altered wall carbohydrate composition. We also found that the effects of cpr5 on trichome size and endoreplication of trichome nuclear DNA were epistatic to the effects of mutations in triptychon (try) or overexpression of GLABRA3, indicating that these trichome developmental regulators are dependant on CPR5 function for their effects on trichome expansion and endoreplication.

Conclusion

Our results suggest that CPR5 is unlikely to be a specific regulator of pathogen response pathways or senescence, but rather functions either in cell wall biogenesis or in multiple cell signaling or transcription response pathways.
Interactions between the quality control ubiquitin ligase CHIP and ubiquitin conjugating enzymes
Authors: Xu Zhen , Kohli Ekta , Devlin Karl I , Bold Michael , Nix Jay C , Misra Saurav
Published: May 2008

Background

Ubiquitin (E3) ligases interact with specific ubiquitin conjugating (E2) enzymes to ubiquitinate particular substrate proteins. As the combination of E2 and E3 dictates the type and biological consequence of ubiquitination, it is important to understand the basis of specificity in E2:E3 interactions. The E3 ligase CHIP interacts with Hsp70 and Hsp90 and ubiquitinates client proteins that are chaperoned by these heat shock proteins. CHIP interacts with two types of E2 enzymes, UbcH5 and Ubc13-Uev1a. It is unclear, however, why CHIP binds these E2 enzymes rather than others, and whether CHIP interacts preferentially with UbcH5 or Ubc13-Uev1a, which form different types of polyubiquitin chains.

Results

The 2.9 Å crystal structure of the CHIP U-box domain complexed with UbcH5a shows that CHIP binds to UbcH5 and Ubc13 through similar specificity determinants, including a key S-P-A motif on the E2 enzymes. The determinants make different relative contributions to the overall interactions between CHIP and the two E2 enzymes. CHIP undergoes auto-ubiquitination by UbcH5 but not by Ubc13-Uev1a. Instead, CHIP drives the formation of unanchored polyubiquitin by Ubc13-Uev1a. CHIP also interacts productively with the class III E2 enzyme Ube2e2, in which the UbcH5- and Ubc13-binding specificity determinants are highly conserved.

Conclusion

The CHIP:UbcH5a structure emphasizes the importance of specificity determinants located on the long loops and central helix of the CHIP U-box, and on the N-terminal helix and loops L4 and L7 of its cognate E2 enzymes. The S-P-A motif and other specificity determinants define the set of cognate E2 enzymes for CHIP, which likely includes several Class III E2 enzymes. CHIP's interactions with UbcH5, Ube2e2 and Ubc13-Uev1a are consistent with the notion that Ubc13-Uev1a may work sequentially with other E2 enzymes to carry out K63-linked polyubiquitination of CHIP substrates.
Evaluation of metabolic syndrome in adults of Talca city, Chile
Authors: Mujica Veronica , Leiva Elba , Icaza Gloria , Diaz Nora , Arredondo Miguel , Moore-Carrasco Rodrigo , Orrego Roxana , Vásquez Marcela , Palomo Ivan
Published: May 2008

Objective-

Insulin resistance (IR) is an important risk factor for type 2 Diabetes Mellitus (DM2) and cardiovascular disease (CVD). Metabolic Syndrome (MS) is a clustering of metabolic alterations associated to IR; however, there is no international consensus for defining its diagnosis. Our objective was to evaluate the prevalence and characteristics of MS identified by the ATP III and IDF criteria in adults from Talca city.

Research and methods-

We studied 1007 individuals, aged 18–74, and residents from Talca. MS subjects were defined according to ATP III (three altered factors) and IDF criteria (patients with waist circumference >80/90 cm (W/M) and two others altered factors).

Results-

The prevalence of metabolic syndrome according to the IDF and ATP III criteria was 36.4% and 29.5%, respectively after adjustment for age and sex. The agreement for both criteria was 89%. The prevalence in men was higher than in women for both MS definitions, although not significant. MS probability increased with age, and the highest risk was in the 57–68 age group (ATP-MS) and 53–72 age group (IDF-MS). Hypertension, high triglycerides and abdominal obesity are the most frequent alterations in MS.

Conclusion-

MS prevalence in adults was higher when diagnosed with IDF than with ATP criterion; in both, age is directly related with the MS presence. The MS subjects showed higher levels of blood pressure, waist circumference and plasma triglycerides. Considering our results, it is worrisome that one third of our population has a high risk of developing DM2 and CVD in the future.
Environmental enrichment has no effect on the development of dopaminergic and GABAergic fibers during methylphenidate treatment of early traumatized gerbils
Authors: Brummelte Susanne , Grund Thorsten , Moll Gunther H , Teuchert-Noodt Gertraud , Dawirs Ralph R
Published: May 2008

It is widely believed, that environmental factors play a crucial role in the etiology and outcome of psychiatric diseases such as Attention-Deficit/Hyperactivity Disorder (ADHD). A former study from our laboratory has shown that both methylphenidate (MP) and handling have a positive effect on the dopaminergic fiber density in the prefrontal cortex (PFC) of early traumatized gerbils (Meriones unguiculatus). The current study was performed to investigate if enriched environment during MP application has an additional influence on the dopaminergic and GABAergic fiber densities in the PFC and amygdala in this animal model.

Animals received a single early dose of methamphetamine (MA; 50 mg/kg; i.p.) on postnatal day (PD) 14, which is known to cause multiple changes in the subsequent development of several neurotransmitter systems including the dopaminergic systems, and were then treated with oral daily applications of MP (5 mg/kg) from PD30–60. Animals treated this way were either transferred to an enriched environment after weaning (on PD30) or were kept under impoverished rearing conditions.

There was no effect of an enriched environment on the dopaminergic or GABAergic fiber density neither in the PFC nor in the amygdala. With regard to former studies these results underline the particular impact of MP in the treatment of ADHD.
Rare ileal localisation of angiolipoma presenting as chronic haemorrhage and severe anaemia: a case report
Authors: Della Volpe Nicola , Bianco Luigi , Bonuso Claudio , Annecchiarico Mario , Di Silverio Pierino , Caiazza Assunta
Published: May 2008

Introduction

Angiolipomas are frequently observed benign tumours. They have a typical vascular component and are often located in subcutaneous tissues, and more rarely, in the gastrointestinal tract.

Case presentation

We report an uncommon case of an angiolipoma found in the lower portion of the small bowel of an 80-year-old man who was undergoing evaluation for chronic anaemia. A standardised diagnostic pathway was followed. Endoscopic and radiological findings were negative. The diagnosis was finally established with the aid of capsule endoscopy. The case we report is the first in the literature of an angiolipoma without specific painful symptoms. In fact, the patient did not complain of abdominal pain or alvus changes, and abdominal examination did not suggest an expansive process. The endoscopic study performed with the capsule identified the lesion as the cause of the ingravescent anaemia. Intra-operative histological examination of the lesion made it possible to avoid a major surgical procedure and assured a short postoperative course for the patient.

Conclusion

This report focuses on the importance of correct pre- and/or intra-operative histological diagnosis in order to offer the best therapeutic choice. An angiolipoma was suspected in this case, even though they are rarely located in the ileum.
Interactions with apoptotic but not with necrotic neutrophils increase parasite burden in human macrophages infected withLeishmania amazonensis
Authors: Afonso Lilian , Borges Valéria M , Cruz Heloísa , Ribeiro-Gomes Flávia L , DosReis George A , Dutra Alberto Noronha , Clarêncio Jorge , de Oliveira Camila I , Barral Aldina , Barral-Netto Manoel , Brodskyn Cláudia I
Published: May 2008

Neutrophils are involved in the initial steps of most responses to pathogens. In the present study, we evaluated the effects of the interaction of apoptotic vs. necrotic human neutrophils on macrophage infection by Leishmania amazonensis. Phagocytosis of apoptotic, but not viable, neutrophils by Leishmania-infected macrophages led to an increase in parasite burden via a mechanism dependent on TGF-β1 and PGE2. Conversely, infected macrophages’ uptake of necrotic neutrophils induced killing of L. amazonensis. Leishmanicidal activity was dependent on TNF-α and neutrophilic elastase. Nitric oxide was not involved in the killing of parasites, but the interaction of necrotic neutrophils with infected macrophages resulted in high superoxide production, a process reversed by catalase, an inhibitor of reactive oxygen intermediate production. Initial events after Leishmania infection involve interactions with neutrophils; we demonstrate that phagocytosis of these cells in an apoptotic or necrotic stage can influence the outcome of infection, driving either parasite survival or destruction.
Assessing 2-Month Clinical Prognosis in Hospitalized Patients With Advanced Solid Tumors
Authors: Barbot Anne-Claire , Mussault Pascale , Ingrand Pierre , Tourani Jean-Marc
Published: May 2008

Purpose

The aim of this study was to assess clinical, laboratory, and subjective (patient's preferences) prognostic factors in hospitalized patients with advanced solid tumors.

Patients and Methods

This prospective study surveyed 177 patients from two French hospitals who had not reached the stage of active dying but had an estimated survival of less than 6 months (median survival, 58 days).

Results

Univariate analysis showed that 10 of the 13 clinical and laboratory factors reported in the literature affected survival at 2 months. Poor prognostic factors were number of metastatic sites, cerebral metastasis, low Karnofsky index, dyspnea at rest, anorexia, edema, confusion, low serum albumin, extremely high leukocyte counts, and high lactate dehydrogenase (LDH) levels. The patient's desire to continue curative treatment was also associated with survival. The multivariate analysis selected four independent criteria: Karnofsky index (in three classes: ≤ 30%, 40% to 60%, or ≥ 70%), number of metastatic sites (≥ two or < two), low serum albumin (in three classes: ≤ 24, 24 to 33, and ≥ 33 g/L), and LDH concentration (≥ 600 IU or < 600 IU). The combination of these four criteria assessed prognosis better than the Karnofsky index alone, producing three prognostic profiles: one with short survival (< 2 months: no patient survived to 4 months); one with an expectation of intermediate survival (25% were alive at 4 months), and a final group surviving for several months (80% were alive at 4 months).

Conclusion

The prognostic profiles defined by combinations of these four factors may be potentially useful but need further validation before their application in the daily practice.
Sex Hormone-Binding Globulin in Fish Gills Is a Portal for Sex Steroids Breached by Xenobiotics
Authors: Miguel-Queralt Solange , Hammond Geoffrey L.
Published: May 2008

As in most vertebrates, plasma sex hormone-binding globulin (SHBG) is produced in fish liver and regulates sex steroid access to target tissues. Low levels of SHBG mRNA are present in zebra fish gills but are unlikely to account for the high amounts of immunoreactive SHBG in filaments and lamellae. Although the uptake of steroids by fish from water has been reported to correlate with their affinity for SHBG, it is not known how this occurs. Our studies of zebra fish SHBG have revealed its preference for biological active androgen (testosterone), as well as for androstenedione, a sex steroid precursor that also acts as a pheromone in some fish. In addition to natural steroids, zebra fish SHBG has a high affinity for synthetic steroids, such as ethinylestradiol and progestins (levonorgestrel and norethindrone), that are present in waste water systems. Because steroids can pass across fish gills, we examined whether SHBG serves as a portal for natural and synthetic steroids controlling their flux between the blood and aquatic environment. The results indicate that SHBG ligands are rapidly and specifically removed from water by the fish through their gills, whereas the accumulated steroids are released slowly. The capacity of fish to sequester SHBG ligands from water is similar between sexes, independent of size, and characterized by a wide dynamic range. We conclude that SHBG controls the flux of sex steroids across fish gills and that this highly specialized function can be hijacked by xenobiotic ligands of fish SHBGs.
Intrahypothalamic Angiogenesis Induced by Osmotic Stimuli Correlates with Local Hypoxia: A Potential Role of Confined Vasoconstriction Induced by Dendritic Secretion of Vasopressin
Authors: Alonso Gérard , Gallibert Evelyne , Lafont Chrystel , Guillon Gilles
Published: May 2008

We have previously shown that hyperosmotic stimulation of adult Wistar rats induces local angiogenesis within hypothalamic magnocellular nuclei, in relation to the secretion of vascular endothelial growth factor (VEGF) by the magnocellular neurons. The present study aimed at understanding how osmotic stimulus relates to increased VEGF secretion. We first demonstrate a correlation between increased VEGF secretion and local hypoxia. Osmotic stimulation is known to stimulate the metabolic activity of hypothalamic magnocellular neurons producing arginine vasopressin (AVP) and to increase the secretion of AVP, both by axon terminals into the circulation and by dendrites into the extracellular space. In AVP-deficient Brattleboro rats, the dramatic activation of magnocellular hypothalamic neurons failed to induce hypoxia, VEGF expression, or angiogenesis, suggesting a major role of hypothalamic AVP. A possible involvement of dendritic AVP release is supported by the findings that 1) hypoxia and angiogenesis were not observed in non osmotically stimulated Wistar rats in which circulating AVP was increased by the prolonged infusion of exogenous AVP, 2) contractile arterioles afferent to the magnocellular nuclei were strongly constricted by the perivascular application of AVP via V1a receptors (V1a-R) stimulation, and 3) after the intracerebral or ip administrations of selective V1a-R antagonists to osmotically stimulated rats, hypothalamic hypoxia and angiogenesis were or were not inhibited, respectively. Together, these data strongly suggest that the angiogenesis induced by osmotic stimulation relates to tissue hypoxia resulting from the constriction of local arterioles, via the stimulation of perivascular V1a-R by AVP locally released from dendrites.
Estrogen Receptor β Isoform-Specific Induction of Transforming Growth Factor β-Inducible Early Gene-1 in Human Osteoblast Cells: An Essential Role for the Activation Function 1 Domain
Authors: Hawse John R. , Subramaniam Malayannan , Monroe David G. , Hemmingsen Amanda H. , Ingle James N. , Khosla Sundeep , Oursler Merry Jo , Spelsberg Thomas C.
Published: May 2008

The estrogen receptors (ER) α and β are important ligand-mediated transcription factors known to play significant biological roles in numerous tissues including bone. Despite the high homology shared by these receptors, recent studies have suggested that their function is largely unique. Although these receptors have been studied in detail for more than a decade, little data exist concerning the mechanisms by which these two proteins regulate distinct sets of genes. Using the TGFβ-inducible early gene-1 (TIEG) as a model, we demonstrate that TIEG is rapidly induced in response to estrogen in osteoblasts by ERβ, but not ERα. We have identified the regulatory elements utilized by ERβ and have demonstrated that ERβ recruits steroid receptor coactivator (SRC)1 and SRC2 to this regulatory region. Additionally, deletion of the ERβ-activation function 1 (AF1) domain drastically decreases the estrogen induction of TIEG. Through the use of chimeric receptors, we have demonstrated that the AF1 domain of ERβ is responsible for recruiting SRC1 and SRC2 and inducing the expression of TIEG in osteoblasts. Finally, SRC1, but not SRC2, is essential for TIEG induction by ERβ. Overall, these data demonstrate that the estrogen induction of TIEG is ERβ specific and that the AF1 domain of ERβ confers this specificity. Finally, a novel and important role for ERβ’s AF1 is implicated in the recruitment of specific coactivators, suggesting that the AF1 may play a significant role in conferring the differences in regulation of gene expression by these two receptors.
Becoming Saraguro: Ethnogenesis in the Context of Inca and Spanish Colonialism
Authors: Ogburn Dennis E.
Published: May 2008

The processes of ethnogenesis in the Andes of the sixteenth century were structured by the different approaches to ethnic identities taken by the Inca and Spanish societies that dominated the region in succession. The Incas enforced boundaries and restricted transculturation, favoring vertical integration of Andean peoples with the state; the Spaniards removed those barriers and emphasized commonalities, favoring a horizontal integration of social groups with each other. This structuring of ethnogenesis is illustrated by Saraguro, Ecuador, where people of disparate ethnic affiliation created a new ethnic identity within the changing contexts of colonial rule. Within these administrative contexts, the particular conditions pertaining to Saraguro, including the history of settlement in the region and the economic conditions during Spanish rule, motivated people to actively change their social identities. Ultimately, Saraguro ethnogenesis was one of the available options whereby indigenous populations could reinterpret existing Andean structures of ethnicity to address the radical challenges of the changing colonial conditions of the sixteenth century.
Ethos, Poetics, and the Literary Public Sphere
Authors: Randall David
Published: May 2008

In Habermasian theory, the bourgeois public sphere was preceded by a literary public sphere whose favored genres revealed the interiority of the self and emphasized an audience-oriented subjectivity. This essay argues that the association of this early modern literary discourse with the ancient public sphere proceeds from their common origin in the historically continuous intellectual tradition of European rhetoric. Ancient rhetoric, which also constituted the ancient public sphere, entered into ancient, medieval, and Renaissance rhetorical poetics; this last, transformed by the anonymizing effects of print culture and the philosophy of skepticism, and by the consequent development of the autonomous narrator, produced the discourse of the early modern literary public sphere. The emergence of this discourse derived particularly from transformations in the concepts of ethos and auctoritas. A crucial prerequisite of this evolution was the shift in the presumed medium of European rhetorical poetics, from orality to writing to print. This argument has consequences for Habermas's general account of communicative rationality and is intended to suggest an alternate theoretical framework, in which the European rhetorical tradition replaces communicative rationality.
Abusive Narratives: Antjie Krog, Rian Malan, and the Transmission of Violence
Authors: Osinubi Taiwo Adetunji
Published: May 2008

In appraisals of Antjie Krog's Country of My Skull, critics reiterate the failures of the South African Truth and Reconciliation Commission (TRC) and criticize Krog's use of victim testimonies. Critics have paid particular attention to the ways in which Krog moves between multiple subject positions as a white South African woman, a journalist, and an Afrikaner. These conflictual positionings are, in part, held responsible for what is seen as her inability to deal critically with the failures of the TRC. While there is certainly merit to these readings of Krog, this essay explores methods of reading Krog's memoir beyond her controversial use of testimonies. As a radio journalist, Krog captures the importance of media processes in constituting sites of witnessing. Specifically, she underlines the importance of the broadcast system that carried out the testifying voice and created communities of listeners. In reading Country of My Skull alongside Rian Malan's My Traitor's Heart, another contentious memoir about apartheid, I suggest that narratives reporting the aftermath of violence on people may inherently always betray victims since writers and readers invariably move to forms of closure. It is important then that readerly sensibilities to apparatuses of transmission are interrogated.
Francophone Egyptian Nationalists, Anti-British Discourse, and European Public Opinion, 1885-1910: The Case of Mustafa Kamil and Ya'qub Sannu'
Authors: Fahmy Ziad
Published: May 2008

This article analyzes how Egyptian nationalists utilized a European propaganda campaign aimed at combating and delegitimizing British colonial rule. In particular, it focuses on Ya'qub Sannu”s (1839-1912) and Mustafa Kamil's (1874-1908) political activities in late-nineteenth- to early-twentieth-century France. Aside from writing dozens of newspaper articles and letters appearing in the French press, both men conducted interviews, made countless speeches, and held many conferences and presentations throughout France and Europe in their continuing attempts at externally forcing a resolution to the Egyptian question. In examining many of these discourses, this article takes into account Sannu”s and Kamil's manipulations of European colonial rivalries, their repeated Francophile appeals, and their frequent exploitation of Anglophobic discourse. Through examining some of the “foreign policy” resistance strategies of colonized intellectuals, the article expands the geographic playing field of colonial-colonized encounters and contestations from the colonies to the heart of the metropole.
Computing Globally Optimal Solutions for Single-Row Layout Problems Using Semidefinite Programming and Cutting Planes
Authors: Anjos Miguel F. , Vannelli Anthony
Published: May 2008

This paper is concerned with the single-row facility layout problem (SRFLP). A globally optimal solution to the SRFLP is a linear placement of rectangular facilities with varying lengths that achieves the minimum total cost associated with the (known or projected) interactions between them. We demonstrate that the combination of a semidefinite programming relaxation with cutting planes is able to compute globally optimal layouts for large SRFLPs with up to 30 facilities. In particular, we report the globally optimal solutions for two sets of SRFLPs previously studied in the literature, some of which have remained unsolved since 1988.
Biases in Valuation vs. Usage of Innovative Product Features
Authors: Meyer Robert J. , Zhao Shenghui , Han Jin K.
Published: May 2008

We investigate biases in product valuation and usage decisions that arise when consumers consider a new generation of a product that offers an expanded set of capabilities of uncertain value. Two experiments using a novel computer game show evidence of a valuation-usage disparity: Participants display a high willingness to pay for a new version of the game that offers a new set of controls, but fail to fully exercise the option to use these controls after purchase. This discrepancy is attributed to a fundamental difference in how new capabilities are valued at the time of purchase versus use. Consumer usage decisions appear to be driven by such myopic concerns as a desire to avoid short-term learning costs, whereas purchase decisions often fail to take into account the factors that drive usage, and are further inflated by global optimism in the future usefulness of new capabilities. We show that this lack of foresight can be explained by an intertemporal judgment model in which consumers attempt to value the option to use new capabilities as would be prescribed by economic theory, but are prone to hyperbolic discounting in their temporal valuation of present versus future costs and benefits.
Necrotizing Meningoencephalitis in Five Chihuahua Dogs
Authors: Higgins R. J. , Dickinson P. J. , Kube S. A. , Moore P. F. , Couto S. S. , Vernau K. M. , Sturges B. K. , Lecouteur R. A.
Published: May 2008

An acute to chronic idiopathic necrotizing meningoencephalitis was diagnosed in 5 Chihuahua dogs aged between 1.5 and 10 years. Presenting neurologic signs included seizures, blindness, mentation changes, and postural deficits occurring from 5 days to 5.5 months prior to presentation. Cerebrospinal fluid analyses from 2 of 3 dogs sampled were consistent with an inflammatory disease. Magnetic resonance imaging of the brain of 2 dogs demonstrated multifocal loss or collapse of cortical gray/white matter demarcation hypointense on T1-weighted images, with T2-weighted hyperintensity and slight postcontrast enhancement. Multifocal asymmetrical areas of necrosis or collapse in both gray and white matter of the cerebral hemispheres was seen grossly in 4 brains. Microscopically in all dogs, there was a severe, asymmetrical, intensely cellular, nonsuppurative meningoencephalitis usually with cystic necrosis in subcortical white matter. There were no lesions in the mesencephalon or metencephalon except in 1 dog. Immunophenotyping defined populations of CD3, CD11d, CD18, CD20, CD45, CD45 RA, and CD79a immunoreactive inflammatory cells varying in density and location but common to acute and chronic lesions. In fresh frozen lesions, both CD1b,c and CD11c immunoreactive dendritic antigen-presenting cells were also identified. Immunoreactivity for canine distemper viral (CDV) antigen was negative in all dogs. The clinical signs, distribution pattern, and histologic type of lesions bear close similarities to necrotizing meningoencephalitis as described in series of both Pug and Maltese breed dogs and less commonly in other breeds.
Noncongophilic Fibrillary Glomerulonephritis in a Cat
Authors: Cavana P. , Capucchio M. T. , Bovero A. , Ripanti D. , Catalano D. , Scaglione F. E. , Miller J. , Blunden T. , Farca A. M.
Published: May 2008

This report describes an uncommon case of nonamyloidotic fibrillary glomerulonephritis. A 5-year-old female European cat was presented with nephrotic syndrome. Serum biochemistry and urinalysis revealed a mild increase in cholesterol, low total protein, severe hypoalbuminemia, and high proteinuria with a high protein-to-creatinine ratio. An histologic examination revealed an interstitial nephritis and a diffuse glomerulonephritis, with multifocal thickening of the Bowman's capsule. Transmission electron microscopy showed widespread fibrillary deposits in the glomerular basement membrane and in the mesangium. These fibrils ranged between 18 and 26 nm in diameter and were Congo red negative, which allowed their differentiation from amyloid. Immunohistochemistry demonstrated expression for immunoglobulin M (IgM) and immunoglobulin G (IgG) within the mesangium. Renal deposits of Congo red-negative amyloid-like fibrils have been described in humans, horses, monkeys, and dogs. This is the first report of noncongophilic fibrillary glomerulopathy in a cat.
Association between ESR2 Genetic Variants and Risk of Myocardial Infarction
Authors: Domingues-Montanari Sophie , Subirana Isaac , Tomás Marta , Marrugat Jaume , Sentí Mariano
Published: May 2008

Background: Environmental and genetic factors contribute to the development of complex diseases such as myocardial infarction (MI), the leading cause of death in men and women. Women develop MI approximately 10 years later than men, a difference that could be explained by the genes coding for the estrogen receptors. Single nucleotide polymorphisms (SNPs) in the ESR2 gene may affect susceptibility for MI in a sex-dependent manner.

Methods: A nested case-control design was used to analyze 3 polymorphisms of the ESR2 gene and their associated haplotypes in 710 myocardial infarction cases from the REGICOR (Registre Gironí del Corazón) study and 2379 controls randomly selected in a representative population of a Spanish cross-sectional study.

Results: The rs1271572 T allele was significantly more common in patients who developed MI (P < 0.001). No association was observed for rs1256049 or rs4986938. Assuming a dominant model of inheritance, the association, as determined by logistic multivariate regression after adjustment for conventional cardiac risk factors, remained statistically significant in men [odds ratio (OR) 1.65, 95% CI 1.18–2.30; P = 0.003) but not in women (P = 0.754). A very common haplotype encompassing the rs1271572 variant was also associated with the risk of MI in the overall population (OR 1.41, 95% CI 1.06–1.87; P = 0.020) and in men (OR 1.57, 95% CI 1.12–2.21; P = 0.009).

Conclusions: The rs1271572 SNP T variant was associated with increased risk of MI in a Spanish population, and this association was found to be limited to men only. Sex differences in the genetic risk merit further investigation.
Utility of Oligonucleotide Array–Based Comparative Genomic Hybridization for Detection of Target Gene Deletions
Authors: Wong Lee-Jun C , Dimmock David , Geraghty Michael T , Quan Richard , Lichter-Konecki Uta , Wang Jing , Brundage Ellen K , Scaglia Fernando , Chinault A Craig
Published: May 2008

Background: Direct DNA sequencing is the primary clinical technique for identifying mutations in human disease, but sequencing often does not detect intragenic or whole-gene deletions. Oligonucleotide array–based comparative genomic hybridization (CGH) is currently in clinical use to detect major changes in chromosomal copy number.

Methods: A custom oligonucleotide-based microarray was constructed to provide high-density coverage of an initial set of 130 nuclear genes involved in the pathogenesis of metabolic and mitochondrial disorders. Standard array CGH procedures were used to test patient DNA samples for regions of copy number change. Sequencing of regions of predicted breakpoints in genomic DNA and PCR analysis were used to confirm oligonucleotide array CGH data.

Results: Oligonucleotide array CGH identified intragenic exonic deletions in 2 cases: a heterozygous single-exon deletion of 4.5 kb in the SLC25A13 gene [solute carrier family 25, member 13 (citrin)] in an individual with citrin deficiency and a homozygous 10.5-kb deletion of exons 13–17 in the ABCB11 gene [PFIC2, ATP-binding cassette, sub-family B (MDR/TAP), member 11] in a patient with progressive familial intrahepatic cholestasis. In 2 females with OTC deficiency, we also found 2 large heterozygous deletions of approximately 7.4 Mb and 9 Mb on the short arm of the X chromosome extending from sequences telomeric to the DMD gene [dystrophin (muscular dystrophy, Duchenne and Becker types)] to sequences within or centromeric to the OTC gene (ornithine carbamoyltransferase).

Conclusions: These examples illustrate the successful use of custom oligonucleotide arrays to detect either whole-gene deletions or intragenic exonic deletions. This technology may be particularly useful as a complementary diagnostic test in the context of a recessive disease when only one mutant allele is found by sequencing.
Risk group chest X-ray for the early detection of lung cancer
Authors: Kovács Gábor
Published: May 2008

Magyarországon a gümőkór elleni szervezett küzdelem egyik legfontosabb eleme a mellkasi röntgenvizsgálaton alapuló évenkénti kötelező lakosságszűrés bevezetése volt. A hetvenes években megközelítően a teljes felnőttnépesség részt vett tüdőszűrésen. A tbc epidemiológiai helyzetének javulásával egyre nagyobb jelentőséggel bír a tüdőrákos betegeknek a szűrővizsgálat „melléktermékeként” történő korai felfedezése. A jövőben a kiemelési hatékonyság érdekében a súlyt a rizikócsoport vizsgálatára kell helyeznünk. Ez a tüdőrák esetében a negyvenévesnél idősebb dohányosok évenkénti ajánlott mellkasi röntgenvizsgálatát jelentheti. Az ajánlott vizsgálat előnyeinek bizonyítására elvégeztük a budapesti tüdőrák-prevalencia retrospektív elemzését. 2511 beteg adatai alapján megállapítottuk, hogy az öt évnél tovább élő tüdőrákos betegek 60%-át fedezték fel szűrővizsgálattal, szemben a panasszal felfedezettek 40%-ával. A szűréssel kiemeltek körében 34% volt az operábilitási ráta, míg a panasszal felfedezetteknek csak a 14%-át lehetett megoperálni. Megállapítottuk, hogy a radikális reszekciós műtét elvégzése valódi többlettúlélési esélyt jelent e betegek számára. Ezt az operált betegek kedvezőbb – három-négy éves – túlélése igazolja. Igaz ugyanakkor az is, hogy a későbbiekben, a kialakuló recidívák miatt a tüdőrák mortalitása nem javul a céllakosság körében. A jelenlegi kiemelési adatok ismeretében ez évente 5–600 beteg számára jelent reálisan többlettúlélési esélyt. Az ajánlott rizikócsoportok (>40 év, dohányosok) mellkasi röntgenvizsgálata esetén az operábilitási ráta további javulásával 1100–1200 beteg kaphatná meg ezt az esélyt.
Angiotensin II Type 1 Receptor Signaling Contributes to Synaptophysin Degradation and Neuronal Dysfunction in the Diabetic Retina
Authors: Kurihara Toshihide , Ozawa Yoko , Nagai Norihiro , Shinoda Kei , Noda Kousuke , Imamura Yutaka , Tsubota Kazuo , Okano Hideyuki , Oike Yuichi , Ishida Susumu
Published: May 2008

OBJECTIVE—Pathogenic mechanisms underlying diabetes-induced retinal dysfunction are not fully understood. The aim of the present study was to show the relationship of the renin-angiotensin system (RAS) with the synaptic vesicle protein synaptophysin and neuronal activity in the diabetic retina.

RESEARCH DESIGN AND METHODS—C57BL/6 mice with streptozotocin-induced diabetes were treated with the angiotensin II type 1 receptor (AT1R) blocker telimsartan or valsartan, and retinal function was analyzed by electroretinography. Retinal production of the RAS components and phosphorylation of ERK (extracellular-signal regulated kinase) were examined by immunoblotting. Retinal mRNA and protein levels of synaptophysin were measured by quantitative RT-PCR and immunoblot analyses, respectively. In vitro, synaptophysin levels were also evaluated using angiotensin II–stimulated PC12D neuronal cells cultured with or without the inhibition of ERK signaling or the ubiquitin-proteasome system (UPS).

RESULTS—Induction of diabetes led to a significant increase in retinal production of angiotensin II and AT1R together with ERK activation in the downstream of AT1R. AT1R blockade significantly reversed diabetes-induced electroretinography changes and reduction of synaptophysin protein, but not mRNA, levels in the diabetic retina. In agreement with the AT1R-mediated posttranscriptional downregulation of synaptophysin in vivo, in vitro application of angiotensin II to PC12D neuronal cells caused the UPS–mediated degradation of synaptophysin protein via AT1R, which proved to be induced by ERK activation.

CONCLUSIONS—These data indicate the first molecular evidence of the RAS-induced synaptophysin degradation and neuronal dysfunction in the diabetic retina, suggesting the possibility of the AT1R blockade as a novel neuroprotective treatment for diabetic retinopathy.
Consequences of Lipid Droplet Coat Protein Downregulation in Liver Cells
Authors: Bell Ming , Wang Hong , Chen Hui , McLenithan John C. , Gong Da-Wei , Yang Rong-Zee , Yu Daozhan , Fried Susan K. , Quon Michael J. , Londos Constantine , Sztalryd Carole
Published: May 2008

OBJECTIVE—Accumulation of intracellular lipid droplets (LDs) in non-adipose tissues is recognized as a strong prognostic factor for the development of insulin resistance in obesity. LDs are coated with perilipin, adipose differentiation–related protein, tail interacting protein of 47 kd (PAT) proteins that are thought to regulate LD turnover by modulating lipolysis. Our hypothesis is that PAT proteins modulate LD metabolism and therefore insulin resistance.

RESEARCH DESIGN AND METHODS—We used a cell culture model (murine AML12 loaded with oleic acid) and small interfering RNA to directly assess the impact of PAT proteins on LD accumulation, lipid metabolism, and insulin action. PAT proteins associated with excess fat deposited in livers of diet-induced obese (DIO) mice were also measured.

RESULTS—Cells lacking PAT proteins exhibited a dramatic increase in LD size and a decrease in LD number. Further, the lipolytic rate increased by ∼2- to 2.5-fold in association with increased adipose triglyceride lipase (ATGL) at the LD surface. Downregulation of PAT proteins also produced insulin resistance, as indicated by decreased insulin stimulation of Akt phosphorylation (P < 0.001). Phosphoinositide-dependent kinase-1 and phosphoinositide 3-kinase decreased, and insulin receptor substrate-1 307 phosphorylation increased. Increased lipids in DIO mice livers were accompanied by changes in PAT composition but also increased ATGL, suggesting a relative PAT deficiency.

CONCLUSIONS—These data establish an important role for PAT proteins as surfactant at the LD surface, packaging lipids in smaller units and restricting access of lipases and thus preventing insulin resistance. We suggest that a deficiency of PAT proteins relative to the quantity of ectopic fat could contribute to cellular dysfunction in obesity and type 2 diabetes.
"Subaltern Nationalism" and the West Berlin Anti-Authoritarians
Authors: Hosek Jennifer Ruth
Published: May 2008

The West Berlin anti-authoritarians around Rudi Dutschke employed a notion of subaltern nationalism inspired by independence struggles in the global South and particularly by post 1959 Cuba to legitimate their loosely understood plans to recreate West Berlin as a revolutionary island. Responding to Che Guevara's call for many Vietnams, they imagined this Northern metropolis as a Focus spreading socialism of the third way throughout Europe, a conception that united their local and global aims. In focusing on their interpretation of societal changes and structures in Cuba, the anti-authoritarians deemphasized these plans' potential for violence. As a study of West German leftists in transnational context, this article suggests the limitations of confining analyses of their projects within national or Northern paradigms. As a study of the influence of the global South on the North in a non-(post)colonial situation, it suggests that such influence is greater than has heretofore been understood.