bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between Plasma Angiopoietin-Like Protein 3 and Arterial Wall Thickness in Healthy Subjects
Authors: Hatsuda Sawako , Shoji Tetsuo , Shinohara Kayo , Kimoto Eiji , Mori Katsuhito , Fukumoto Shinya , Koyama Hidenori , Emoto Masanori , Nishizawa Yoshiki
Published: December 2006

Background: Angiopoietin-like protein 3 (ANGPTL3) is a liver-derived plasma protein that modulates plasma triglyceride clearance, angiogenesis and atherosclerosis in experimental models. So far, no study has examined its role in atherosclerosis in human subjects. We evaluated the possible association between plasma ANGPTL3 level and carotid artery intima-media thickness (CA-IMT) and femoral artery intima-media thickness (FA-IMT) in healthy human subjects. Methods: The subjects were 381 healthy volunteers. Plasma ANGPTL3 was determined by a specific ELISA. CA-IMT and FA-IMT were measured by high-resolution B-mode ultrasonography. Results: The plasma ANGPTL3 level was 764 ± 291 ng/ml (mean ± SD). CA-IMT showed a significant positive correlation with plasma ANGPTL3 and other classical risk factors such as age, blood pressure, and plasma glucose and lipid levels. The positive association between ANGPTL3 and CA-IMT remained significant after adjustment for age, sex, smoking, body mass index, systolic blood pressure, plasma glucose, insulin resistance index, triglyceride, and high-density and low-density lipoprotein cholesterol levels. ANGPTL3 also showed a positive association with FA-IMT independent of these factors. Conclusions: These results demonstrate for the first time that ANGPTL3 is closely associated with arterial wall thickness in human subjects.
Resveratrol, a Polyphenolic Phytostilbene, Inhibits Endothelial Monocyte Chemotactic Protein-1 Synthesis and Secretion
Authors: Cullen John P. , Morrow David , Jin Ying , Curley Brian , Robinson Alex , Sitzmann James V. , Cahill Paul A. , Redmond Eileen M.
Published: December 2006

Background/Aims: Resveratrol is a naturally occurring polyphenol phytoestrogen and one of several constituents of red wine thought to be cardioprotective. We investigated the effect of resveratrol on the expression of the atherogenic chemokine, monocyte chemotactic protein-1 (MCP-1). Methods: Human umbilical vein endothelial cells were stimulated with interleukin-1β (IL-1β) in the absence or presence of resveratrol. MCP-1 levels were determined by ELISA and MCP-1 mRNA was measured. Results: Resveratrol (1–100 µM) dose-dependently inhibited IL-1β-stimulated MCP-1 secretion, with ∼45% inhibition at 50 µM resveratrol. This was a Gi-protein- and NO-dependent effect. Resveratrol also significantly inhibited MCP-1 gene expression in a Gi-protein-dependent but NO-independent manner. While resveratrol had no effect on MCP-1 mRNA degradation, it inhibited MCP-1 promoter activity and reduced nuclear factor ĸB and activator protein-1 binding activity induced by IL-1β. Moreover, while hemoxygenase-1 (HO-1) expression was induced by resveratrol in human umbilical vein endothelial cells, neither treatment with the HO-1 inhibitor tin-protoporphyrin IX nor siRNA-directed knockdown of HO-1 had any effect on the inhibition of MCP-1 mRNA or protein secretion by resveratrol. Conclusion: These data demonstrate an inhibitory effect of resveratrol on MCP-1 synthesis and secretion, mediated via distinct signaling pathways. The inhibition of MCP-1 may represent a novel cardioprotective mechanism of resveratrol.
Particle-Mediated Gene Delivery and Human Skin: Ultrastructural Observations on Stratum Corneum Barrier Structures
Authors: Menon G.K. , Brandsma J.L. , Schwartz P.M.
Published: December 2006

The particle-mediated delivery systems are becoming a clinically relevant tool in dermatology and immunology. We investigated the qualitativeultrastructural morphology of skin following pressure-driven delivery of gold particles to ex vivo human breast skin, at different pressures ranging from 350 to 1,000 psi. Pressures of 800 and 1,000 psi appear to be more effective, as indicated by distribution of particles in the viable epidermis and dermis. Particle bombardment of the skin with gold beads caused microwounds that spanned the stratum corneum (SC). The SC lipids did not reseal these wounds in the SC after 24 h in organ culture. The implications of particle-mediated delivery to permeability barrier functions of the SC are discussed.
The Hemodynamically Significant Ductus Arteriosus in Critically Ill Full-Term Neonates
Authors: Ly Linh G. , Hawes Judith , Whyte Hilary E. , Teixeira Lilian S. , McNamara Patrick J.
Published: December 2006

In premature infants, the clinical effects and management of a hemodynamically significant patent ductus arteriosus (HSDA) are well-described. In full-term neonates the ductus arteriosus (DA) is rarely monitored except in cases of concomitant pulmonary hypertension or duct dependant congenital heart disease. Although systemic–pulmonary shunting commonly occurs in mature infants, coinciding with the normal postnatal fall in pulmonary vascular resistance, cardiac failure in the neonatal period is rarely attributed directly to the DA. In this case series, we report two full-term infants who were initially treated for pulmonary hypertension and myocardial dysfunction but developed clinical, radiographic and two-dimensional echocardiographic evidence of cardiac failure secondary to a large unrestrictive patent DA (PDA). One patient was treated with indomethacin, and, although transductal diameter decreased, there was no clinical benefit. Cardiac failure resolved and myocardial function improved in both cases after PDA ligation. We suggest that PDA be monitored closely in neonates recovering from PPHN who have ongoing oxygenation difficulties or myocardial failure. PDA ligation should be considered an option for full term neonates with cardiac failure secondary to a HSDA when other therapeutic options fail.
Effect of Sulodexide on Albuminuria, NAG Excretion and Glomerular Filtration Response to Dopamine in Diabetic Patients
Authors: Sulikowska B. , Olejniczak H. , Muszyńska M. , Odrowaz-Sypniewska G. , Gaddi A. , Savini C. , Cicero A.F.G. , Laghi L. , Manitius J.
Published: December 2006

Background: Albuminuria is the best and most readily available marker for glomerular damage and progressive renal function loss in patients with diabetic nephropathy. Recently, administration of the oral glycosaminoglycan sulodexide (a mixture of 80% fast-moving heparin and 20% dermatan sulphate) was shown to effectively decrease albumin excretion rate in diabetics with nephropathy. Aims: To evaluate whether the hypoalbuminuric effect of sulodexide is associated with improvement of the renal vascular or tubule function. Methods: Forty-five type 1 diabetic patients, affected by diabetic nephropathy with albuminuria for at least 5 years, were randomly allocated to sulodexide or untreated. Those allocated to sulodexide were given 100 mg of sulodexide daily for 120 days. Renal vascular function (DIR) and N-acetyl-β-D-glucosaminidase (NAG) excretion were estimated before and at the end of the study, the former in thesulodexide group only. DIR was measured as two Crcl lasting 120 min (before and during 2 µg/kg b.w. i.v. dopamine). Results: The analysis of trends during the study demonstrated a marked reduction of albuminuria in the sulodexide group (from 126.1 ± 15.41 to 93.6 ± 13.7 mg/day). DIR rose from 13.2 ± 2.1% to 15.44 ± 1.9% (relative increase: +16.9%), and NAG excretion showed a decreasing trend decreased in the sulodexide group only (from 5.1 ± 0.62 to 4.7 ± 0.40 U/gcreat). Conclusion: The findings presented in this study indicate for the first time that orally available sulodexide may favorably affect the renal vascular function in type 1 diabetic patients with nephropathy and microalbuminuria. The effect of sulodexide on NAG is strongly influenced by the baseline NAG values, with a significant NAG reduction in the patients with the highest baseline NAG values.
HIV Infection among Uganda Women with Cervical Cancer: a Retrospective Study
Authors: Sekirime Wilberforce Kigongo , Gray Ron
Published: December 2006

Objective: To assess whether there is an association between HIV and invasive cervical cancer (ICC). Methodology: A case-control study was conducted in Kampala between 1993 and 1995. 116 women with ICC were matched by age and parity with 116 hospital controls. Participants were tested for HIV and interviewed to assess risk factors for ICC and HIV. The association between HIV and ICC was assessed by conditional logistic regression. Results: HIV prevalence was 18% among cases and 15% among controls. The odds of having ICC for HIV-infected patients was 1.27 (95% CI 0.58–2.80) when compared to controls, and the odds of being infected with HIV was higher in ICC patients aged <33 years (OR = 3.81) when compared to controls of similar age. HIV-infected ICC patients were younger (mean age 35.8 years) compared to 46.5 years in the ICC HIV-negative group (p = 0.021). Conclusion: HIV is associated with an earlier onset of ICC.
Osteoimmunology
Authors: Rauner Martina , Sipos Wolfgang , Pietschmann Peter
Published: December 2006

Osteoimmunology is an interdisciplinary research field combining the exciting fields of osteology and immunology. An observation that contributed enormously to the emergence of osteoimmunology was the accelerated bone loss caused by inflammatory diseases such as rheumatoid arthritis. Receptor activator of nuclear factor ĸB ligand (RANKL), which is the main regulator of osteoclastogenesis, was found to be the primary culprit responsible for the enhanced activation of osteoclasts: activated T cells directly and indirectly increased the expression of RANKL, and thereby promoted osteoclastic activity. Excessive bone loss is not only present in inflammatory diseases but also in autoimmune diseases and cancer. Furthermore, there is accumulating evidence that the very prevalent skeletal disorder osteoporosis is associated with alterations in the immune system. Meanwhile, numerous connections have been discovered in osteoimmunology beyond merely the actions of RANKL. These include the importance of osteoblasts in the maintenance of the hematopoietic stem cell niche and in lymphocyte development as well as the functions of immune cells participating in osteoblast and osteoclast development. Furthermore, research is being done investigating cytokines, chemokines, transcription factors and co-stimulatory molecules which are shared by both systems. Research in osteoimmunology promises the discovery of new strategies and the development of innovative therapeutics to cure or alleviate bone loss in inflammatory and autoimmune diseases as well as in osteoporosis. This review gives an introduction to bone remodeling and the cells governing that process and summarizes the most recent discoveries in the interdisciplinary field of osteoimmunology. Furthermore, an alternative large animal model will be discussed and the pathophysiological alterations of the immune system in osteoporosis will be highlighted.
Effects of Ectodomain Sequences between HR1 and HR2 of F1 Protein on the Specific Membrane Fusion in Paramyxoviruses
Authors: Ren Guijie , Wang Zhiyu , Hu Xiaoyan
Published: December 2006

Objectives: To explore the effects of ectodomain sequences between HR1 and HR2 of F1 protein on the specific interaction with its homologous hemagglutinin-neuraminidase (HN) in paramyxoviruses. Methods: Site-directed mutagenesis was used to obtain mutants containing new enzyme sites on the F genes of Newcastle disease virus (NDV) and human parainfluenza virus (hPIV), and four DNA segments located between the HR1 and HR2 (NDV F-1, hPIV F-1, NDV F-2 and hPIV F-2) were obtained by cutting mutant F genes with specific endonucleases. Gene recombination was used to get chimeric F proteins NDV-C1 and hPIV-C1 by exchanging NDV F-1 and hPIV F-1 each other, and NDV-C2 and hPIV-C2 were also obtained by the same way. All the mutants and chimeric F proteins were co-expressed with their homologous or heterologous HN proteins in eukaryocytes. The fusion functions were assayed with Giemsa staining and reporter gene method for qualitative and quantitative analyses, respectively. The cell surface expression of F proteins was assayed with fluorescence-activated cell sorter (FACS) for quantitative analysis. Results: All the mutants of F proteins had the same functions as their relevant wild types. Chimeric F proteins NDV-C1 and hPIV-C1 had 76.34 and 65.82% of fusion activities, and NDV-C2 and hPIV-C2 had 96.25 and 93.78% of fusion activities, respectively, as compared with their relevant wild types. The analysis of FACS indicated that all the mutants and chimeric F proteins had almost the same expression efficiencies as their relevant wild types. Conclusions: The segments of NDV F-1 and hPIV F-1 were important for their specific membrane fusion, but NDV F-2 and hPIV F-2 were not.
Compositional Bias and Size of Genomes of Human DNA Viruses
Authors: Sewatanon Jaturong , Srichatrapimuk Sirawat , Auewarakul Prasert
Published: December 2006

Genomes of 144 human DNA viruses were analyzed in the aspect of their compositional asymmetry. DNA viruses were divided into two groups according to their genome sizes. The analysis revealed that the level of guanine and cytosine (GC content) in the coding sequences of small genome DNA viruses was significantly lower than that of large genome DNA viruses. Because small genome viruses replicate their genomes using cellular enzymes, while large genome viruses use their own enzymes for genome replication, the two groups of viruses may be under different mutational bias and/or selection pressure. In these viruses, GC content at the third codon position correlated with GC content at the first and second codon position. However, the relationship in small genome DNA viruses was weaker than that in large genome DNA viruses, suggesting that their genome composition may be more strongly influenced by codon usage preference or restriction on amino acid composition.
Interferon Therapy Improves the Irregular Regeneration of Hepatocytes in Liver in Patients with C-Viral Chronic Hepatitis and Liver Cirrhosis
Authors: Moriyama Mitsuhiko , Matsumura Hiroshi , Oshiro Shu , Nakamura Hitomi , Arakawa Yasuo , Nirei Kazushige , Aoki Hiroshi , Yamagami Hiroaki , Kaneko Miki , Tanaka Naohide , Arakawa Yasuyuki
Published: December 2006

We examined changes in the degree of irregular regeneration (IR) of hepatocytes and the F stage in patients with C-viral chronic hepatitis (CH) and liver cirrhosis (LC) who received interferon (IFN) therapy. The IFN-treated group consisted of 148 C-viral CH and LC patients; the IFN-untreated (UT) group consisted of 42 patients. The liver biopsy specimens were examined histologically, followed by a separate scoring of the degree of IR of hepatocytes which was classified into the following 5 grades and scored (IR score): score 0 (none), 1 (minimal), 2 (mild), 3 (moderate) and 4 (severe). The annual rates of the IR score were –0.593 in sustained virologic responders, –0.188 in sustained biochemical responders, 0.071 in nonresponders and 0.121 in UT patients. The annual rates of the F stage were –0.218 in sustained virologic responders, –0.061 in sustained biochemical responders, 0.123 in nonresponders and 0.157 in UT patients. The cumulative probability of hepatocellular carcinoma (HCC) incidence was significantly higher in groups of IFN-treated patients without improvement of IR scores than in groups with improvement of IR scores. Multivariate analyses revealed that a lack of improvement in the IR score was a cardinal risk factor for the development of HCC in C-viral CH and LC patients. Our data suggest that IFN therapy leads to an improvement in the degree of IR of hepatocytes and thereby influences the development of HCC in patients with CH and LC.
Inhibition of 3-Hydroxy-3-Methylglutaryl Coenzyme A (HMG CoA) Reductase Blunts Factor VIIa/Tissue Factor and Prothrombinase Activities via Effects on Membrane Phosphatidylserine
Authors: Dietzen Dennis J. , Page Keith L. , Tetzloff Tina A. , Bohrer Alan , Turk John
Published: December 2006

Objective—

3-Hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors (statins) exhibit antithrombotic properties that are independent of reductions in circulating LDL cholesterol. We hypothesized that these antithrombotic properties are mediated by membrane alterations secondary to disrupted lipid metabolism.

Methods and Results—

EA.hy926 cells were incubated in the presence of 1 μmol/L atorvastatin supplemented with fetal bovine serum or lipid-depleted serum mixtures. Lipid restriction alone had no effect on cell lipid composition but when atorvastatin was included, phosphatidylserine, sphingomyelin, and cholesterol were reduced by 50% while ceramide content decreased by 70%. These changes in lipid composition did not alter the association of decay accelerating factor or tissue factor with lipid rafts. Atorvastatin in combination with lipid restriction reduced factor VIIa/tissue factor activity by as much as 75% but did not alter tissue factor expression. Prothrombinase activity was reduced to an extent similar to factor VIIa/tissue factor. Mevalonic acid but not LDL reversed the observed changes in lipid content and prothrombinase activity induced by atorvastatin. These findings were confirmed in primary cells.

Conclusions—

Inhibition of HMG-CoA reductase limits exposure of phosphatidylserine at the cell surface by restricting the cellular pool of mevalonate-derived isoprenoids. This membrane alteration restricts the activity of proteolytic enzyme complexes that propagate the coagulation cascade.
Functional Arterial and Venous Fate Is Determined by Graded VEGF Signaling and Notch Status During Embryonic Stem Cell Differentiation
Authors: Lanner Fredrik , Sohl Marcus , Farnebo Filip
Published: December 2006

Objective—

The aim of this work was to develop a mouse embryonic stem (ES) cell system addressing the early specification of the developing vasculature into functional arteries and veins.

Methods and Results—

ES cells were differentiated 4 days on collagen-type IV coated dishes to obtain Flk1
+
endothelial precursors. Sub-culture of these precursors for additional 4 days robustly generated, in a VEGF dose-dependent manner, mature endothelial cells. Arterial marker genes were specifically expressed in cultures differentiated with high VEGF concentration whereas the venous marker gene COUP-TFII was upregulated in endothelial cells induced through low and intermediate VEGF concentrations. This VEGF-dependent arterialization could be blocked by inhibition of Notch resulting in an arterial to venous fate switch. Functional and morphological studies, ie, measurement of sprout length, pericyte recruitment, and interleukin-I-induced leukocyte adhesion, further confirmed their arterial and venous identity.

Conclusions—

We conclude that endothelial cells with distinct molecular, morphological, and functional characteristics of arteries and veins can be derived through in vitro differentiation of ES cells in a VEGF dose-dependent and Notch-regulated manner.
Effect of Nicardipine Prolonged-Release Implants on Cerebral Vasospasm and Clinical Outcome After Severe Aneurysmal Subarachnoid Hemorrhage
Authors: Barth Martin , Capelle Hans-Holger , Weidauer Stephan , Weiss Christel , Münch Elke , Thomé Claudius , Luecke Thomas , Schmiedek Peter , Kasuya Hidetoshi , Vajkoczy Peter
Published: December 2006

Background and Purpose—

The purpose of this study was to investigate the effect of nicardipine prolonged-release implants (NPRIs) on cerebral vasospasm and clinical outcome after severe subarachnoid hemorrhage.

Methods—

Thirty-two patients with severe subarachnoid hemorrhage and undergoing aneurysm clipping were included into this single center, randomized, double-blind trial. Sixteen patients received NPRIs implanted into the basal cisterns in direct contact to the exposed proximal blood vessels; in 16 control patients, the basal cisterns were opened and washed out only without leaving implants. Angiography was performed preoperatively and at day 8±1. Computed tomography imaging was analyzed for the incidence of territorial infarcts unrelated to surgery. Patient outcome was assessed using the modified Rankin and National Institute of Health Stroke scales.

Results—

The incidence of angiographic vasospasm in proximal vessel segments was significantly reduced after implantation of NPRIs (73% control versus 7% NPRIs). Significant differences occurred also for the majority of distal vessel segments. Computed tomography scans revealed a lower incidence of delayed ischemic lesions (47% control versus 14% NPRIs). The NPRI group demonstrated more favorable modified Rankin and National Institute of Health Stroke scales as well as a significantly lower incidence of deaths (38% control versus 6% NPRIs).

Conclusions—

Implantation of NPRIs reduces the incidence of cerebral vasospasm and delayed ischemic deficits and improves clinical outcome after severe subarachnoid hemorrhage.
Repositioning Students in Initial Teacher Preparation
Authors: Cook-Sather Alison , Youens Bernadette
Published: December 2006

Discussions of learning to teach for social justice generally focus on the social commitments, institutional structures, course content, and pedagogical processes that support prospective teachers. Missing from this array of foci is a consideration of how school students are positioned within teacher preparation and how their positioning and participation can inform prospective teachers’ preparation to teach for social justice. In this article, the authors present a comparative descriptive analysis of two projects, one based in the United States and one based in England, that provide opportunities through which prospective secondary teachers are prepared to teach for social justice through direct dialogue with secondary students focused on issues of teaching and learning.
Researching Teacher Education Practices
Authors: Loughran John
Published: December 2006

This article explores the nature of self-study of teacher education practices by examining what self-study is and how it might be conducted and reported. In working through these ideas, the article makes an argument for the need for learning through self-study to be documented in ways that might not only be accessible to others but also meaningful for their practice in teaching about teaching. Although the term self-study suggests a singular and individual approach to researching practice, the reality is that self-studies are dramatically strengthened by drawing on alternative perspectives and reframing of situations, thus data, ideas, and input that necessitate moving beyond the self. Moving beyond the self also matters because a central purpose in self-study is uncovering deeper understandings of the relationship between teaching about teaching and learning about teaching. This article argues a need for these deeper understandings to be developed in ways that enhance an articulation of a pedagogy of teacher education.
Navigating Sites for Narrative Inquiry
Authors: Clandinin D. Jean , Pushor Debbie , Orr Anne Murray
Published: December 2006

Narrative inquiry is a methodology that frequently appeals to teachers and teacher educators. However, this appeal and sense of comfort has advantages and disadvantages. Some assume narrative inquiries will be easy to design, live out, and represent in storied formats in journals, dissertations, or books. For the authors, though, narrative inquiry is much more than the telling of stories. There are complexities surrounding all phases of a narrative inquiry and, in this article, the authors pay particular attention to thinking about the design of narrative inquiries that focus on teachers’ and teacher educators’ own practices. They outline three commonplaces and eight design elements for consideration in narrative inquiry. They illustrate these elements using recently completed narrative inquiries. In this way, the authors show the complex dimensions of narrative inquiry, a kind of inquiry that requires particular kinds of wakefulness.
Patients with adenosine deaminase deficiency surviving after hematopoietic stem cell transplantation are at high risk of CNS complications
Authors: Hönig Manfred , Albert Michael H. , Schulz Ansgar , Sparber-Sauer Monika , Schütz Catharina , Belohradsky Bernd , Güngör Tayfun , Rojewski Markus T. , Bode Harald , Pannicke Ulrich , Lippold Dominique , Schwarz Klaus , Debatin Klaus-Michael , Hershfield Michael S. , Friedrich Wilhelm
Published: December 2006

Adenosine deaminase (ADA) deficiency is a systemic metabolic disease that causes an autosomal recessive variant of severe combined immunodeficiency (SCID) and less consistently other complications including neurologic abnormalities. Hematopoietic stem cell transplantation (HSCT) is able to correct the immunodeficiency, whereas control of nonimmunologic complications has not been extensively explored. We applied HSCT in 15 ADA-deficient patients consecutively treated at our institutions since 1982 and analyzed long-term outcome. Seven patients received transplants without conditioning from HLA-matched family donors (MFDs); the other 8 patients received conditioning and were given transplants either from HLA-mismatched family donors (MMFDs; n = 6) or from matched unrelated donors (MUDs; n = 2). At a mean follow-up period of 12 years (range, 4-22 years), 12 patients are alive with stable and complete immune reconstitution (7 of 7 after MFD, 4 of 6 after MMFD, and 1 of 2 after MUD transplantation). Six of 12 surviving patients show marked neurologic abnormalities, which include mental retardation, motor dysfunction, and sensorineural hearing deficit. We were unable to identify disease or transplantation-related factors correlating with this divergent neurologic outcome. The high rate of neurologic abnormalities observed in long-term surviving patients with ADA deficiency indicates that HSCT commonly fails to control CNS complications in this metabolic disease.
Identification of potential CepR regulated genes using a cep box motif-based search of the Burkholderia cenocepacia genome
Authors: Chambers Catherine E , Lutter Erika I , Visser Michelle B , Law Peggy PY , Sokol Pamela A
Published: December 2006

Background

The Burkholderia cenocepacia CepIR quorum sensing system has been shown to positively and negatively regulate genes involved in siderophore production, protease expression, motility, biofilm formation and virulence. In this study, two approaches were used to identify genes regulated by the CepIR quorum sensing system. Transposon mutagenesis was used to create lacZ promoter fusions in a cepI mutant that were screened for differential expression in the presence of N-acylhomoserine lactones. A bioinformatics approach was used to screen the B. cenocepacia J2315 genome for CepR binding site motifs.

Results

Four positively regulated and two negatively regulated genes were identified by transposon mutagenesis including genes potentially involved in iron transport and virulence. The promoter regions of selected CepR regulated genes and site directed mutagenesis of the cepI promoter were used to predict a consensus cep box sequence for CepR binding. The first-generation consensus sequence for the cep box was used to identify putative cep boxes in the genome sequence. Eight potential CepR regulated genes were chosen and the expression of their promoters analyzed. Six of the eight were shown to be regulated by CepR. A second generation motif was created from the promoters of these six genes in combination with the promoters of cepI, zmpA, and two of the CepR regulated genes identified by transposon mutagenesis. A search of the B. cenocepacia J2315 genome with the new motif identified 55 cep boxes in 65 promoter regions that may be regulated by CepR.

Conclusion

Using transposon mutagenesis and bioinformatics expression of twelve new genes have been determined to be regulated by the CepIR quorum sensing system. A cep box consensus sequence has been developed based on the predicted cep boxes of ten CepR regulated genes. This consensus cep box has led to the identification of over 50 new genes potentially regulated by the CepIR quorum sensing system.
Tissue microarray analysis reveals a tight correlation between protein expression pattern and progression of esophageal squamous cell carcinoma
Authors: Xue Li-yan , Hu Nan , Song Yong-mei , Zou Shuang-mei , Shou Jian-zhong , Qian Lu-xia , Ren Li-qun , Lin Dong-mei , Tong Tong , He Zu-gen , Zhan Qi-min , Taylor Philip R , Lu Ning
Published: December 2006

Background

The development of esophageal squamous cell carcinoma (ESCC) progresses a multistage process, collectively known as precursor lesions, also called dysplasia (DYS) and carcinoma in situ (CIS), subsequent invasive lesions and final metastasis. In this study, we are interested in investigating the expression of a variety of functional classes of proteins in ESCC and its precursor lesions and characterizing the correlation of these proteins with ESCC malignant progression.

Methods

Fas, FADD, caspase 8, CDC25B, fascin, CK14, CK4, annexin I, laminin-5γ2 and SPARC were analyzed using immunohistochemistry on tissue microarray containing 205 ESCC and 173 adjacent precursor lesions as well as corresponding normal mucosa. To confirm the immunohistochemical results, three proteins, fascin, CK14 and laminin-5γ2, which were overexpressed in ESCC on tissue microarray, were detected in 12 ESCC cell lines by Western blot assay.

Results

In ESCC and its precursor lesions, FADD, CDC25B, fascin, CK14, laminin-5γ2 and SPARC were overexpressed, while Fas, caspase 8, CK4 and annexin I were underexpressed. The abnormalities of these proteins could be classified into different groups in relation to the stages of ESCC development. They were "early" corresponding to mild and moderate DYS with overexpression of fascin, FADD and CDC25B and underexpression of Fas, caspase 8, CK4 and annexin I, "intermediate" to severe DYS and CIS with overexpression of FADD and CK14, and "late" to invasive lesions (ESCC) and to advanced pTNM stage ESCC lesions with overexpression of CK14, laminin-5γ2 and SPARC.

Conclusion

Analyzing the protein expression patterns of Fas, FADD, caspase 8, CDC25B, fascin, CK14, CK4, annexin I, laminin-5γ2 and SPARC would be valuable to develop rational strategies for early detection of lesions at risk in advance as well as for prevention and treatment of ESCC.
Multiplexed expression and screening for recombinant protein production in mammalian cells
Authors: Chapple Susan DJ , Crofts Anna M , Shadbolt S Paul , McCafferty John , Dyson Michael R
Published: December 2006

Background

A variety of approaches to understanding protein structure and function require production of recombinant protein. Mammalian based expression systems have advantages over bacterial systems for certain classes of protein but can be slower and more laborious. Thus the availability of a simple system for production and rapid screening of constructs or conditions for mammalian expression would be of great benefit. To this end we have coupled an efficient recombinant protein production system based on transient transfection in HEK-293 EBNA1 (HEK-293E) suspension cells with a dot blot method allowing pre-screening of proteins expressed in cells in a high throughput manner.

Results

A nested PCR approach was used to clone 21 extracellular domains of mouse receptors as CD4 fusions within a mammalian GATEWAY expression vector system. Following transient transfection, HEK-293E cells grown in 2 ml cultures in 24-deep well blocks showed similar growth kinetics, viability and recombinant protein expression profiles, to those grown in 50 ml shake flask cultures as judged by western blotting. Following optimisation, fluorescent dot blot analysis of transfection supernatants was shown to be a rapid method for analysing protein expression yielding similar results as western blot analysis. Addition of urea enhanced the binding of glycoproteins to a nitrocellulose membrane. A good correlation was observed between the results of a plate based small scale transient transfection dot blot pre-screen and successful purification of proteins expressed at the 50 ml scale.

Conclusion

The combination of small scale multi-well plate culture and dot blotting described here will allow the multiplex analysis of different mammalian expression experiments enabling a faster identification of high yield expression constructs or conditions prior to large scale protein production. The methods for parallel GATEWAY cloning and expression of multiple constructs in cell culture will also be useful for applications such as the generation of receptor protein microarrays.
Expression and function of the OX40/OX40L costimulatory pair during herpes stromal keratitis
Authors: Lepisto Andrew J , Xu Min , Yagita Hideo , Weinberg Andrew D , Hendricks Robert L
Published: December 2006

Herpes stromal keratitis (HSK) is an immunopathological disease regulated by Th1 CD4 T cells, which require APC and costimulation within the infected cornea to mediate disease. Recent studies suggest the OX40:OX40 ligand (OX40L) interaction enhances effector cell cytokine secretion at inflammatory sites. OX40+ cells were detected in HSV-1-infected mouse corneas as early as 3 days postinfection (dpi), prior to the onset of HSK, and their frequency increased through 15 dpi, when all mice exhibited severe HSK. OX40L+ cells were first detected at 7 dpi, coincident with the initiation of HSK. It is interesting that the OX40L+ cells did not coexpress MHC Class II or the dendritic cell (DC) marker CD11c. Our findings demonstrate rapid infiltration of activated (OX40+) CD4+ T cells into HSV-1-infected corneas and expression of OX40L on MHC Class II-negative cells but surprisingly, not on MHC Class II+ CD11c+ DC, which are present in the infected corneas and required for HSK. Moreover, neither local nor systemic treatment of mice with a blocking antibody to OX40L or with a blocking fusion protein altered the course of HSK significantly, possibly as a result of a lack of OX40L expression on functional APC.
Estrogen selectively regulates chemokines in murine splenocytes
Authors: Lengi Andrea J , Phillips Rebecca A , Karpuzoglu Ebru , Ahmed S Ansar
Published: December 2006

Estrogen has striking effects on immunity and inflammatory autoimmune conditions. One potential mechanism of estrogen-induced regulation of immunity and inflammatory autoimmune conditions is by altering the secretion of chemokines by lymphocytes, an aspect not well addressed thus far. We found that estrogen has marked, but differential, effects on the secretion of chemokines from activated splenocytes. Estrogen treatment significantly increased the secretion of MCP-1, MCP-5, eotaxin, and stromal cell-derived factor 1β from Con A-activated splenocytes when compared with placebo-treated controls, and it had no effects on the levels of RANTES, thymus and activation-regulated chemokine, and keratinocyte-derived chemokine (KC) at 24 h. A kinetic analysis showed that chemokines tended to increase with stimulation time, but only MCP-1 and MCP-5 showed a biological trend of increasing in splenocytes from estrogen-treated mice, and KC was decreased significantly in estrogen-treated splenocytes at 18 h. Estrogen did not affect the protein levels of chemokine receptors CCR1 or CCR2 at 24 h. Estrogen-induced alterations in the levels of MCP-1 and MCP-5 are mediated, in part, by IFN-γ, as estrogen treatment of IFN-γ null mice, unlike wild-type mice, did not up-regulate these chemokines. However, addition of recombinant IFN-γ resulted in markedly increased secretion of MCP-1 and MCP-5 only in the cells derived from estrogen-treated mice. These studies provide novel data indicating that estrogen may promote inflammatory conditions by altering the levels of chemokines, providing evidence for an additional mechanism by which estrogens can regulate inflammation.
United Nations Measures to Stop Violence against Women
Authors: SANDIS EVA E.
Published: December 2006

Abstract:  This article consists of a brief overview of the involvement by the United Nations (UN) and nongovernmental organizations (NGOs) in worldwide efforts to expose and prevent violence against women. It begins with a depiction of the types of gender‐based violence in contemporary society. Then follows a short history of the institutions and mechanisms created by the UN and civil society to prevent domestic and public violence against women. It concludes with a sketch of ongoing UN/NGO efforts to build on the momentum of the last decade, and suggests the challenges this presents to each and all of us in the new millennium.
International Sexual Harassment
Authors: SIGAL JANET
Published: December 2006

Abstract:  This paper on international sexual harassment begins with a presentation of the definitions, models, and consequences of sexual harassment. Following this discussion, a description is given of a nine‐country research program that examined reactions to academic sexual harassment. A brief review of incidence studies and international laws related to sexual harassment are also included.
Cyberspace Violence against Girls and Adolescent Females
Authors: CHISHOLM JUNE F.
Published: December 2006

Abstract:  Children and adolescents today are the first generation raised in a society in which technological literacy is essential for effective citizenship in the 21st century. With many more youth using digital technologies for educational and recreational purposes, there has been an increase in social problems in cyberspace, exposing them to different forms of cyberviolence. This article gives an overview of the developments in cyberspace, describes different types of cyberviolence, and focuses on cyberbullying among girls and adolescent females as both victims and perpetrators of cyberbullying. At‐risk online activities among girls and adolescent females as well as strategies to promote cybersafety are presented. Current research and future directions for research are reviewed.
Battered Woman Syndrome
Authors: WALKER LENORE E.A.
Published: December 2006

Abstract:  The construct of Battered Woman Syndrome (BWS) has been conceptualized as a subcategory of posttraumatic stress disorder (PTSD). It is composed of the following symptoms: (a) re‐experiencing the battering as if it were reoccurring even when it is not, (b) attempts to avoid the psychological impact of battering by avoiding activities, people, and emotions, (c) hyperarousal or hypervigilance, (d) disrupted interpersonal relationships, (e) body image distortion or other somatic concerns, and (f) sexuality and intimacy issues. This article presents empirical data derived from administering the Battered Woman Syndrome Questionnaire (BWSQ) to women of four countries—United States, Spain, Greece, and Russia. The data support a theory of BWS.
Gender‐Based Violence
Authors: RUSSO NANCY FELIPE , PIRLOTT ANGELA
Published: December 2006

Abstract: The United Nations has identified gender‐based violence against women as a global health and development issue, and a host of policies, public education, and action programs aimed at reducing gender‐based violence have been undertaken around the world. This article highlights new conceptualizations, methodological issues, and selected research findings that can inform such activities. In addition to describing recent research findings that document relationships between gender, power, sexuality, and intimate violence cross‐nationally, it identifies cultural factors, including linkages between sex and violence through media images that may increase women's risk for violence, and profiles a host of negative physical, mental, and behavioral health outcomes associated with victimization including unwanted pregnancy and abortion. More research is needed to identify the causes, dynamics, and outcomes of gender‐based violence, including media effects, and to articulate how different forms of such violence vary in outcomes depending on cultural context.
Identification of Regions within the F Domain of the Human Estrogen Receptor α that Are Important for Modulating Transactivation and Protein-Protein Interactions
Authors: Koide Akiko , Zhao Changqing , Naganuma Misuzu , Abrams Judith , Deighton-Collins Sarah , Skafar Debra F. , Koide Shohei
Published: December 2006

The estrogen receptor (ER)α is a biologically and clinically important ligand-modulated transcription factor. The F domain of the ERα modulates its functions in a ligand-, promoter-, and cell-specific manner. To identify the region(s) responsible for these functions, we characterized the effects of serial truncations within the F domain. We found that truncating the last 16 residues of the F domain altered the activity of the human ERα (hERα) on an estrogen response element-driven promoter in response to estradiol or 4-hydroxytamoxifen (4-OHT), its sensitivity to overexpression of the coactivator steroid receptor coactivator-1 in mammalian cells, and its interaction with a receptor-interacting domain of the coactivator steroid receptor coactivator-1 or engineered proteins (“monobodies”) that specifically bind to ERα/ligand complexes in a yeast two-hybrid system. Most importantly, the ability of the ER to induce pS2 was reduced in MDA-MB-231 cells stably expressing this truncated ER vs. the wild-type ER. The region includes a distinctive segment (residues 579–584; LQKYYIT) having a high content of bulky and/or hydrophobic amino acids that was previously predicted to adopt a β-strand-like structure. As previously reported, removal of the entire F domain was necessary to eliminate the agonist activity of 4-OHT. In addition, mutation of the vicinal glycine residues between the ligand-binding domain and F domains specifically reduced the 4-OHT-dependent interactions of the hERα ligand-binding domain and F domains with monobodies. These results show that regions within the F domain of the hERα selectively modulate its activity and its interactions with other proteins.
Distinct Wnt signaling pathways have opposing roles in appendage regeneration
Authors: Stoick-Cooper Cristi L. , Weidinger Gilbert , Riehle Kimberly J. , Hubbert Charlotte , Major Michael B. , Fausto Nelson , Moon Randall T.
Published: December 2006

In contrast to mammals, lower vertebrates have a remarkable capacity to regenerate complex structures damaged by injury or disease. This process,termed epimorphic regeneration, involves progenitor cells created through the reprogramming of differentiated cells or through the activation of resident stem cells. Wnt/β-catenin signaling regulates progenitor cell fate and proliferation during embryonic development and stem cell function in adults,but its functional involvement in epimorphic regeneration has not been addressed. Using transgenic fish lines, we show that Wnt/β-catenin signaling is activated in the regenerating zebrafish tail fin and is required for formation and subsequent proliferation of the progenitor cells of the blastema. Wnt/β-catenin signaling appears to act upstream of FGF signaling, which has recently been found to be essential for fin regeneration. Intriguingly, increased Wnt/β-catenin signaling is sufficient to augment regeneration, as tail fins regenerate faster in fish heterozygous for a loss-of-function mutation in axin1, a negative regulator of the pathway. Likewise, activation of Wnt/β-catenin signaling by overexpression of wnt8 increases proliferation of progenitor cells in the regenerating fin. By contrast, overexpression of wnt5b(pipetail) reduces expression of Wnt/β-catenin target genes,impairs proliferation of progenitors and inhibits fin regeneration. Importantly, fin regeneration is accelerated in wnt5b mutant fish. These data suggest that Wnt/β-catenin signaling promotes regeneration,whereas a distinct pathway activated by wnt5b acts in a negative-feedback loop to limit regeneration.
Antagonistic roles of full-length N-cadherin and its soluble BMP cleavage product in neural crest delamination
Authors: Shoval Irit , Ludwig Andreas , Kalcheim Chaya
Published: December 2006

During neural crest ontogeny, an epithelial to mesenchymal transition is necessary for cell emigration from the dorsal neural tube. This process is likely to involve a network of gene activities, which remain largely unexplored. We demonstrate that N-cadherin inhibits the onset of crest delamination both by a cell adhesion-dependent mechanism and by repressing canonical Wnt signaling previously found to be necessary for crest delamination by acting downstream of BMP4. Furthermore, N-cadherin protein,but not mRNA, is normally downregulated along the dorsal tube in association with the onset of crest delamination, and we find that this process is triggered by BMP4. BMP4 stimulates cleavage of N-cadherin into a soluble cytoplasmic fragment via an ADAM10-dependent mechanism. Intriguingly, when overexpressed, the cytoplasmic N-cadherin fragment translocates into the nucleus, stimulates cyclin D1 transcription and crest delamination, while enhancing transcription of β-catenin. CTF2 also rescues the mesenchymal phenotype of crest cells in ADAM10-inhibited neural primordia. Hence, by promoting its cleavage, BMP4 converts N-cadherin inhibition into an activity that is likely to participate, along with canonical Wnt signaling, in the stimulation of neural crest emigration.
Noncoding RNA synthesis and loss of Polycomb group repression accompanies the colinear activation of the human HOXA cluster
Authors: Sessa Luca , Breiling Achim , Lavorgna Giovanni , Silvestri Laura , Casari Giorgio , Orlando Valerio
Published: December 2006

The ratio of noncoding to protein coding DNA rises with the complexity of the organism, culminating in nearly 99% of nonprotein coding DNA in humans. Nevertheless, a large portion of these regions is transcribed, creating the alleged paradox that noncoding RNA (ncRNA) represents the largest output of the human genome. Such a complex scenario may include epigenetic mechanisms where ncRNAs would be involved in chromatin regulation. We have investigated the intergenic, noncoding transcriptomes of mammalian HOX clusters. We show that “opposite strand transcription” from the intergenic spacer regions in the human HOXA cluster correlates with the activity state of adjacent HOXA genes. This noncoding transcription is regulated by the retinoic acid morphogen and follows the colinear activation pattern of the cluster. Opening of the cluster at sites of activation of intergenic transcripts is accompanied by changes in histone modifications and a loss of interaction with Polycomb group (PcG) repressive complexes. We propose that noncoding transcription is of fundamental importance for the opening and maintenance of the active state of HOX clusters.