bluuebunny/crossref_metadata_2025 huggingface dataset:
Methylation Induced Gene Silencing of HtrA3 in Smoking-Related Lung Cancer
Authors: Beleford Daniah , Liu Zhixue , Rattan Ramandeep , Quagliuolo Lucio , Boccellino Mariarosaria , Baldi Alfonso , Maguire Jacie , Staub Julie , Molina Julian , Shridhar Viji
Published: January 2010

Purpose: Some 85% of lung cancers are smoking related. Here, we investigate the role of serine protease HtrA3 in smoking-related lung cancer.

Experimental Design: We assess HtrA3 methylation and its corresponding expression in the human bronchial cell line BEAS-2B following cigarette smoke carcinogen treatment, in lung cancer cell lines and in primary lung tumors from light, moderate, and heavy smokers. We also show the effects of HtrA3 downregulation on MTT reduction and clonogenic survival with etoposide and cisplatin treatment and the corresponding effects of HtrA3 re-expression during treatment.

Results: We show for the first time that HtrA3 expression is reduced or completely lost in over 50% of lung cancer cell lines and primary lung tumors from heavy smokers. Treatment of HtrA3-deficient cell lines with 5-aza-2′-deoxycytidine resulted in a dose-dependent increase in HtrA3 transcription. Further, sequence analysis of bisulfite-modified DNA from lung cancer cell lines and from primary lung tumors showed an increased frequency of methylation within the first exon of HtrA3 with a corresponding loss of HtrA3 expression, particularly in tumors from smokers. In BEAS-2B, treatment with the cigarette smoke carcinogen 4-(methylnitrosamino)-I-(3-pyridyl)-1-butanone resulted in HtrA3 downregulation with a corresponding increase in methylation. Additional studies indicate resistance to etoposide and cisplatin cytotoxicity as a functional consequence of HtrA3 loss. Finally, immunohistochemical analysis of primary lung tumors revealed a strong correlation between low HtrA3 expression and heavy smoking history.

Conclusions: Collectively, these results suggest that cigarette smoke–induced methylation of HtrA3 could contribute to the etiology of chemoresistant disease in smoking-related lung cancer. Clin Cancer Res; 16(2); 398–409
Mechanisms of Ascorbate-Induced Cytotoxicity in Pancreatic Cancer
Authors: Du Juan , Martin Sean M. , Levine Mark , Wagner Brett A. , Buettner Garry R. , Wang Sih-han , Taghiyev Agshin F. , Du Changbin , Knudson Charles M. , Cullen Joseph J.
Published: January 2010

Purpose: Pharmacologic concentrations of ascorbate may be effective in cancer therapeutics. We hypothesized that ascorbate concentrations achievable with i.v. dosing would be cytotoxic in pancreatic cancer for which the 5-year survival is <3%.

Experimental Design: Pancreatic cancer cell lines were treated with ascorbate (0, 5, or 10 mmol/L) for 1 hour, then viability and clonogenic survival were determined. Pancreatic tumor cells were delivered s.c. into the flank region of nude mice and allowed to grow at which time they were randomized to receive either ascorbate (4 g/kg) or osmotically equivalent saline (1 mol/L) i.p. for 2 weeks.

Results: There was a time- and dose-dependent increase in measured H2O2 production with increased concentrations of ascorbate. Ascorbate decreased viability in all pancreatic cancer cell lines but had no effect on an immortalized pancreatic ductal epithelial cell line. Ascorbate decreased clonogenic survival of the pancreatic cancer cell lines, which was reversed by treatment of cells with scavengers of H2O2. Treatment with ascorbate induced a caspase-independent cell death that was associated with autophagy. In vivo, treatment with ascorbate inhibited tumor growth and prolonged survival.

Conclusions: These results show that pharmacologic doses of ascorbate, easily achievable in humans, may have potential for therapy in pancreatic cancer. Clin Cancer Res; 16(2); 509–20
Interleukin 13 Mediates Signal Transduction through Interleukin 13 Receptor α2 in Pancreatic Ductal Adenocarcinoma: Role of IL-13 Pseudomonas Exotoxin in Pancreatic Cancer Therapy
Authors: Shimamura Takeshi , Fujisawa Toshio , Husain Syed R. , Joshi Bharat , Puri Raj K.
Published: January 2010

Purpose: Interleukin-13 receptor α2 (IL-13Rα2) is a tumor antigen that is overexpressed in certain human tumors. However, its significance and expression in pancreatic cancer is not known. It is also not known whether IL-13 can signal through IL-13Rα2 in cancer.

Experimental Design: The expression of IL-13Rα2 was assessed in pancreatic cancer samples by immunohistochemistry and in cell lines by flow cytometry and reverse transcription-PCR. The role of IL-13Rα2 was examined by IL-13–induced signaling in pancreatic cancer cell lines. IL-13Rα2–positive tumors were targeted by IL-13PE cytotoxin in vitro and in vivo in an orthotopic murine model of human pancreatic cancer.

Results: Of the pancreatic tumor samples 71% overexpressed moderate to high-density IL-13Rα2 chain compared with normal pancreatic samples. IL-13 induced transforming growth factor-β1 promoter activity in IL-13Rα2–positive tumor cells and in cells engineered to express IL-13Rα2 but not in IL-13Rα2–negative or RNA interference knockdown cells. c-Jun and c-Fos of the AP-1 family of nuclear factors were activated by IL-13 only in IL-13Rα2–positive cells. In the orthotopic mouse model, IL13-PE significantly decreased tumor growth when assessed by whole-body imaging and prolonged the mean survival time. Similar results were observed in mice xenografted with a surgically resected human pancreatic tumor sample.

Conclusions: These results indicate that IL-13Rα2 is a functional receptor as IL-13 mediates signaling in human pancreatic cancer cell lines. IL-13 causes transforming growth factor-β activation via AP-1 pathway, which may cause tumor induced immunosuppression in the host. In addition, IL13-PE cytotoxin may be an effective therapeutic agent for the treatment of pancreatic cancer. Clin Cancer Res; 16(2); 577–86
Development of Molecularly Targeted Therapies in Hepatocellular Carcinoma: Where Do We Go Now?
Authors: Finn Richard S.
Published: January 2010

Hepatocellular carcinoma (HCC), once considered an orphan disease in the West, has become a global health concern. It is the third leading cause of cancer death worldwide, and its incidence continues to increase. Historically, the development of new systemic agents for advanced HCC has been lacking despite no clear benefit with traditional cytotoxic therapies. Although two randomized studies with sorafenib for the treatment of HCC patients have recently been completed, survival benefits have been modest and highlight the unmet medical need among patients with HCC. Given the clear need, clinical development of novel systemic agents in HCC has begun in earnest. These clinical studies are founded on a growing body of basic and translational science that has identified several potential molecular targets in HCC. The successful development of such targeted agents in the future will be linked to our ability to appropriately select patients for treatment based on their clinical stage (including extent of liver disease and extent of tumor) and on potential predictive markers of response. Here, we review these data in the context of rational drug development in HCC in the front-line setting and in previously treated patients. Clin Cancer Res; 16(2); 390–7.
Vandetanib, Designed to Inhibit VEGFR2 and EGFR Signaling, Had No Clinical Activity as Monotherapy for Recurrent Ovarian Cancer and No Detectable Modulation of VEGFR2
Authors: Annunziata Christina M. , Walker Amanda J. , Minasian Lori , Yu Minshu , Kotz Herbert , Wood Bradford J. , Calvo Katherine , Choyke Peter , Kimm Daniel , Steinberg Seth M. , Kohn Elise C.
Published: January 2010

Purpose: To evaluate clinical activity and target modulation of vandetanib in women with recurrent ovarian cancer.

Experimental Design: A phase II trial of orally administered vandetanib 300 mg daily was designed to include analyses of target inhibition through paired biopsies and dynamic imaging. Core 18-gauge needle biopsies and dynamic contrast-enhanced magnetic resonance imaging were obtained before initiation of therapy and 6 weeks into therapy. Biopsy samples were subjected to reverse-phase protein lysate array endpoint analysis. Cytokine concentrations were measured by enzyme-linked immunosorbent assay in serially collected plasma samples.

Results: Twelve patients entered the study, and accrual was terminated in the first stage because of lack of response or disease stabilization beyond 6 months. Adverse events included rash, diarrhea, and prolonged QT interval corrected for heart rate, but not hypertension. Exploratory analyses showed that epidermal growth factor receptor (EGFR) phosphorylation was reduced in the eight paired biopsy sets obtained; vascular endothelial growth factor (VEGF) receptor-2 phosphorylation was not consistently affected nor were dynamic contrast-enhanced MRI permeability and flow parameters. Serial plasma VEGF concentrations were variable and did not significantly change in the 11 patients assessed.

Conclusions: Vandetanib 300 mg daily monotherapy had no significant clinical benefit in this disease setting. Proteomic analysis of paired biopsies detected both phosphorylated-EGFR and phosphorylated-VEGF receptor-2 in ovarian tumor tissue, but only phosphorylated-EGFR was measurably inhibited by vandetanib. Clin Cancer Res; 16(2); 664–72
Immunoglobulin Heavy Chain Variable Gene Usage and (Super)-antigen Drive in Chronic Lymphocytic Leukemia
Authors: Bühler Andreas , Zenz Thorsten , Stilgenbauer Stephan
Published: January 2010

Increasing evidence supports the prognostic relevance of specific immunoglobulin heavy chain variable (IGHV) genes or stereotyped B-cell receptors (BCR) in chronic lymphocytic leukemia (CLL). The clonotypic BCRs differ in their specificity and affinity toward classical antigens and/or superantigens. The BCR-triggered mechanisms are distinct but could explain in part the different clinical behavior among CLL subgroups. Clin Cancer Res; 16(2); 373–5
Resistance to IFN-α–Induced Apoptosis Is Linked to a Loss of STAT2
Authors: Romero-Weaver Ana L. , Wang Hsiang-Wen , Steen Håkan C. , Scarzello Anthony J. , Hall Veronica L. , Sheikh Faruk , Donnelly Raymond P. , Gamero Ana M.
Published: January 2010

Type I IFNs (IFN-α/β) are pleitropic cytokines widely used in the treatment of certain malignancies, hepatitis B and C, and multiple sclerosis. IFN resistance is a challenging clinical problem to overcome. Hence, understanding the molecular mechanism by which IFN immunotherapy ceases to be effective is of translational importance. In this study, we report that continuous IFN-α stimulation of the human Jurkat variant H123 led to resistance to type I IFN–induced apoptosis due to a loss of signal transducers and activators of transcription 2 (STAT2) expression. The apoptotic effects of IFN-α were hampered as STAT2-deficient cells were defective in activating the mitochondrial-dependent death pathway and ISGF3-mediated gene activation. Reconstitution of STAT2 restored the apoptotic effects of IFN-α as measured by the loss of mitochondrial membrane potential, cytochrome c release from mitochondria, caspase activation, and ultimately cell death. Nuclear localization of STAT2 was a critical event as retention of tyrosine-phosphorylated STAT2 in the cytosol was not sufficient to activate apoptosis. Furthermore, silencing STAT2 gene expression in Saos2 and A375S.2 tumor cell lines significantly reduced the apoptotic capacity of IFN-α. Altogether, we show that STAT2 is a critical mediator in the activation of type I IFN–induced apoptosis. More importantly, defects in the expression or nuclear localization of STAT2 could lessen the efficacy of type I IFN immunotherapy. Mol Cancer Res; 8(1); 80–92
5-Hydroxy-2-Methyl-1,4-Naphthoquinone, a Vitamin K3 Analogue, Suppresses STAT3 Activation Pathway through Induction of Protein Tyrosine Phosphatase, SHP-1: Potential Role in Chemosensitization
Authors: Sandur Santosh K. , Pandey Manoj K. , Sung Bokyung , Aggarwal Bharat B.
Published: January 2010

The activation of signal transducers and activators of transcription 3 (STAT3) has been linked with carcinogenesis through survival, proliferation, and angiogenesis of tumor cells. Agents that can suppress STAT3 activation have potential not only for prevention but also for treatment of cancer. In the present report, we investigated whether 5-hydroxy-2-methyl-1,4-naphthoquinone (plumbagin), an analogue of vitamin K, and isolated from chitrak (Plumbago zeylanica), an Ayurvedic medicinal plant, can modulate the STAT3 pathway. We found that plumbagin inhibited both constitutive and interleukin 6–inducible STAT3 phosphorylation in multiple myeloma (MM) cells and this correlated with the inhibition of c-Src, Janus-activated kinase (JAK)1, and JAK2 activation. Vanadate, however, reversed the plumbagin-induced downregulation of STAT3 activation, suggesting the involvement of a protein tyrosine phosphatase. Indeed, we found that plumbagin induced the expression of the protein tyrosine phosphatase, SHP-1, and silencing of the SHP-1 abolished the effect of plumbagin. This agent also downregulated the expression of STAT3-regulated cyclin D1, Bcl-xL, and vascular endothelial growth factor; activated caspase-3; induced poly (ADP ribose) polymerase cleavage; and increased the sub-G1 population of MM cells. Consistent with these results, overexpression of constitutive active STAT3 significantly reduced the plumbagin-induced apoptosis. When compared with AG490, a rationally designed STAT3/JAK2 inhibitor, plumbagin was found more potent in suppressing the proliferation of cells. Plumbagin also significantly potentiated the apoptotic effects of thalidomide and bortezomib in MM cells. Overall, these results suggest that the plumbagin inhibits STAT3 activation pathway through the induction of SHP-1 and this may mediate the sensitization of STAT3 overexpressing cancers to chemotherapeutic agents.Mol Cancer Res; 8(1); 107–118
Regulation of Expression of Stromal-Derived Factor-1 Receptors: CXCR4 and CXCR7 in Human Rhabdomyosarcomas
Authors: Tarnowski Maciej , Grymula Katarzyna , Reca Ryan , Jankowski Kacper , Maksym Radoslaw , Tarnowska Joanna , Przybylski Grzegorz , Barr Frederic G. , Kucia Magdalena , Ratajczak Mariusz Z.
Published: January 2010

Rhabdomyosarcomas (RMS) express CXCR4 and CXCR7 receptors that bind prometastatic α-chemokine stromal-derived factor-1 (SDF-1). In this report, we analyzed the activity of both promoters in a model of less metastatic human embryonal-RMS cell line (RD) and more metastatic alveolar-like RMS (RD cells transduced with paired box gene 3/forkhead homologue; PAX3-FKHR fusion gene). First, CXCR4 is barely detectable in RD and becomes upregulated in RD/PAX3-FKHR cells. In contrast, CXCR7 highly expressed in RD becomes downregulated in RD/PAX3-FKHR cells. Next, promoter deletion and mutation studies revealed that whereas (a) expression of CXCR4 in RD and RD/PAX3-FKHR cells required nuclear respiratory factor-1 (NRF-1) binding site and (b) was additionally upregulated by direct interaction of NRF-1 with PAX3-FKHR, CXCR7 promoter activity required a proximal nuclear factor-κB–binding motif. The requirement of these factors for CXCR4 and CXCR7 promoter activities was additionally supported after blocking NRF-1 and nuclear factor-κB. Furthermore, CXCR4 expression in PAX3-FKHR+ RMS cells seems to be enhanced because of the interaction of PAX3-FKHR and NRF-1 proteins in the proximal part of the promoter that prevents access of the negative regulator of transcription YY1 to its binding site. Finally, although hypoxia enhances CXCR4 and CXCR7 promoter activity and receptor expression in RD cells, it inhibits CXCR7 expression in RD/PAX3-FKHR cells. In conclusion, SDF-1 binding receptors CXCR4 and CXCR7 are differently regulated in RMS cells. The upregulation of CXCR4 and downregulation of CXCR7 expression by PAX3-FKHR or hypoxia may give SDF-1 an advantage to better engage the CXCR4 receptor, thus increasing RMS motility. Mol Cancer Res; 8(1); 1–14
Bioenergetic Metabolites Regulate Base Excision Repair–Dependent Cell Death in Response to DNA Damage
Authors: Tang Jiang-bo , Goellner Eva M. , Wang Xiao-hong , Trivedi Ram N. , St Croix Claudette M. , Jelezcova Elena , Svilar David , Brown Ashley R. , Sobol Robert W.
Published: January 2010

Base excision repair (BER) protein expression is important for resistance to DNA damage–induced cytotoxicity. Conversely, BER imbalance [DNA polymerase β (Polβ) deficiency or repair inhibition] enhances cytotoxicity of radiation and chemotherapeutic DNA-damaging agents. Whereas inhibition of critical steps in the BER pathway result in the accumulation of cytotoxic DNA double-strand breaks, we report that DNA damage–induced cytotoxicity due to deficiency in the BER protein Polβ triggers cell death dependent on poly(ADP-ribose) (PAR) polymerase activation yet independent of PAR-mediated apoptosis-inducing factor nuclear translocation or PAR glycohydrolase, suggesting that cytotoxicity is not from PAR or PAR catabolite signaling. Cell death is rescued by the NAD+ metabolite β-nicotinamide mononucleotide and is synergistic with inhibition of NAD+ biosynthesis, showing that DNA damage–induced cytotoxicity mediated via BER inhibition is primarily dependent on cellular metabolite bioavailability. We offer a mechanistic justification for the elevated alkylation-induced cytotoxicity of Polβ-deficient cells, suggesting a linkage between DNA repair, cell survival, and cellular bioenergetics. Mol Cancer Res; 8(1); 67–79
FOXM1 Confers Acquired Cisplatin Resistance in Breast Cancer Cells
Authors: Kwok Jimmy M.-M. , Peck Barrie , Monteiro Lara J. , Schwenen Helma D.C. , Millour Julie , Coombes R. Charles , Myatt Stephen S. , Lam Eric W.-F.
Published: January 2010

The transcription factor Forkhead box M1 (FOXM1) is a key regulator of cell proliferation and is overexpressed in many forms of primary cancers, leading to uncontrolled cell division and genomic instability. To address the role of FOXM1 in chemoresistance, we generated a cisplatin-resistant breast cancer cell line (MCF-7-CISR), which had an elevated level of FOXM1 protein and mRNA expression relative to the parental MCF-7 cells. A close correlation was observed between FOXM1 and the expression of its proposed downstream targets that are involved in DNA repair; breast cancer–associated gene 2 (BRCA2) and X-ray cross-complementing group 1 (XRCC1) were expressed at higher levels in the resistant cell lines compared with the sensitive MCF-7 cells. Moreover, cisplatin treatment induced DNA damage repair in MCF-7-CISR and not in MCF-7 cells. Furthermore, the expression of a constitutively active FOXM1 (ΔN-FOXM1) in MCF-7 cells alone was sufficient to confer cisplatin resistance. Crucially, the impairment of DNA damage repair pathways through the small interfering RNA knockdown inhibition of either FOXM1 or BRCA2/XRCC1 showed that only the silencing of FOXM1 could significantly reduce the rate of proliferation in response to cisplatin treatment in the resistant cells. This suggests that the targeting of FOXM1 is a viable strategy in circumventing acquired cisplatin resistance. Consistently, the FOXM1 inhibitor thiostrepton also showed efficacy in causing cell death and proliferative arrest in the cisplatin-resistant cells through the downregulation of FOXM1 expression. Taken together, we have identified a novel mechanism of acquired cisplatin resistance in breast cancer cells through the induction of FOXM1. Mol Cancer Res; 8(1); 24–34
Characterization of Duck Enteritis Virus US6, US7 and US8 Gene
Authors: Zhao Yan , Wang Jun Wei
Published: January 2010

Aims: Duck enteritis virus (DEV) is a member of the family Herpesviridae, the genome of which is not completely analyzed. In order to provide further insights into the genomic organization, we decided to amplify the unknown sequence in the US region since three key glycoproteins are coded in this region. Glycoprotein D encoded by US6 gene is essential for virus entry and plays an important role in protecting animals from lethal challenge. Glycoprotein I and E encoded by US7 and US8 gene are required for cell-to-cell spread. Methods: Single oligonucleotide nested polymerase chain reaction was adopted to amplify the unknown sequence. The open reading frames (ORF) were predicted by Editseq program. Then the sequence was submitted to an online program to search promoter, polyadenylation signal and potential N-glycosylation sites. The phylogenetic analysis was performed by MEGA4.1, while multiple alignments were performed by ClustalX. Results: Three complete ORFs including US6, US7 and US8 were determined. The three genes shared the same polyadenylation signal. Phylogenetic analysis showed that DEV was closed to mardivirus of alphaherpesvirus. Conclusion: These results extend our understanding of the DEV genome and its classification, and also provide further basic knowledge for functional investigations on the proteins in the US region.
Relationship between Regulatory T Cells and the Combination of Pegylated Interferon and Ribavirin for the Treatment of Chronic Hepatitis Type C
Authors: Akiyama Motohisa , Ichikawa Tatuki , Miyaaki Hisamitsu , Motoyoshi Yasuhide , Takeshita Shigeyuki , Ozawa Eisuke , Miuma Satoshi , Shibata Hidetaka , Taura Naota , Nakao Kazuhiko
Published: January 2010

Background/Aim: The frequency of regulatory T cells (Tregs) may be related to persistent hepatitis C virus (HCV) infection. We studied the alteration of the Treg ratio in peripheral blood mononuclear cells (PBMCs) from chronic hepatitis C patients during combination therapy compared with the Treg ratio in liver-infiltrating lymphocytes (LILs) before therapy. Method: The study group consisted of 20 patients who were treatment-naive and had high virus titers of HCV genotype 1. Blood samples were collected prior to treatment and at several time points during treatment. All patients received a liver biopsy prior to treatment. Forkhead box P3 (Foxp3)+, CD3+, CD4+ and CD8+ cells in PBMCs and LILs were stained by specific antibodies. Results: Ten patients had a sustained virological response (SVR), and 10 patients were non-responders. The SVR group had a significant increase in the Foxp3+/CD4+ ratio in PBMCs at 8 and 12 weeks as well as a significant decrease in the Foxp3+/CD4+ ratio and increase in the CD8+/Foxp3+ ratio in LILs. Conclusion: The evaluation of Tregs, a potentially significant factor for persistent HCV infection, in LILs prior to treatment and in PBMCs during treatment could predict the result of combination therapy.
Distribution of Orexin/Hypocretin Immunoreactivity in the Brain of the Lungfishes Protopterus dolloi and Neoceratodus forsteri
Authors: López Jesús M. , Domínguez Laura , Moreno Nerea , Morona Ruth , Joven Alberto , González Agustín
Published: January 2010

Lungfishes are currently considered the closest living relatives of tetrapods and represent an interesting group for the study of evolutionary traits in the transition from fishes to tetrapods. The brains of lungfishes have received little attention in comparative studies probably due to the difficulty of obtaining these unique animals. In the present study the distribution of orexin (hypocretin)-like immunoreactivity was studied in the brain of the African lungfish Protopterus dolloi and the Australian lungfish Neoceratodus forsteri by using antibodies directed against the mammalian orexin-A and orexin-B peptides. Simultaneous detection of orexins and tyrosine hydroxylase or serotonin was used to assess the precise location of the orexins in the brain and to evaluate the possible influence of the orexin system on the monoaminergic cell groups. Although some differences were noted, a common pattern for the distribution of orexins in the two lungfishes studied was observed. In both species, most immunoreactive neurons were observed in the suprachiasmatic nucleus and dorsal hypothalamus. Only in Neoceratodus, however, were important cell populations found in the preoptic area and infundibular hypothalamus, whereas small numbers of faintly reactive neurons were present in the lateral septum and ventral striatum. Fiber labeling was widely distributed in all main brain subdivisions, but was more abundant in regions such as the septum, preoptic area, suprachiasmatic nucleus, lateral hypothalamic area, thalamus, pretectum and tegmentum. Less conspicuous was the innervation of the pallial regions, habenula, optic tectum, rhombencephalic reticular formation and spinal cord. Orexinergic innervation was found in close contact with dopaminergic, noradrenergic and serotoninergic cell groups, homologous to the substantia nigra in the midbrain tegmentum, the locus coeruleus, the nucleus of the solitary tract and the raphe nuclei. Although unique features have been found for lungfishes, the location of orexin immunoreactive elements is largely consistent with that recently reported following a similar approach in amphibians and amniotes, suggesting that the general organization of this peptidergic system occurred in the common ancestor of lungfishes and tetrapods.
Walking for the Assessment of Balance in Healthy Subjects Older than 40 Years
Authors: Spagnuolo Daniel Lucas , Jürgensen Soraia Pilon , Iwama Ângela May , Dourado Victor Zuniga
Published: January 2010

Background: The Berg scale and the timed ‘up and go’ test (TUG) are established measures to assess mobility in frail older adults. As an alternative to self-paced tests to assess aerobic exercise capacity, the incremental shuttle walk test (ISWT) was developed. We hypothesized that ISWT may be useful for the assessment of aerobic capacity and balance simultaneously in healthy adults. Objectives: There are 3 objectives: (1) to evaluate the intra-tester reliability of TUG in healthy subjects; (2) to compare the validity of TUG, ISWT and comfortable gait speed (GS) to evaluate balance assessed by the Berg balance scale, and (3) to evaluate the correlations among these walking tests. Methods: We studied a sample of 64 subjects (82.81% women) aged 40–84 years to assess the intra-tester reliability of TUG. Of these, 21 subjects also performed ISWT, GS and the Berg balance scale. We also assessed height, weight, body mass index, spirometry and reported physical activity. Results: The average time to complete TUG was 7.23 ± 1.27 s. The interclass correlation coefficient of TUG was excellent (0.936; 95% CI: 0.895–0.961). Age (r = 0.36), GS (r = –0.64), GS/height (r = –0.44), ISWT (r = –0.65) and the Berg score (r = –0.65) were correlated with TUG (p < 0.05). The Berg score was significantly (p < 0.05) correlated with GS (r = 0.61) and ISWT (r = 0.61). Moreover, ISWT was mutually related with GS (r = 0.68). We evaluated 2 models of linear regression, using GS and TUG as independent variables in each of them. In the 1st model, GS described 47% of the ISWT variability. In the 2nd, TUG described 42.7% of the ISWT variability. Conclusions: The capacity of walking is related to balance in healthy adults and seniors. Our results suggest the usefulness of ISWT as a new tool for the simultaneous evaluation of the aerobic capacity and balance in healthy subjects. An important part of the ISWT variation was explained by GS and TUG. Secondly, we confirmed the significant influence of age in the TUG performance and the excellent reliability of this field walking test.
Calling strategies of male túngara frogs in response to dynamic playback
Authors: Argo IV  , Goutte  , Kime  , Argo
Published: January 2010

Túngara frogs produce calls of varying complexity that consist of a whine followed by 0–7 chucks. In previous studies using static playbacks, males increase chuck number in response to calls with 1 versus 0 chucks but not in response to 2 or 3 versus 1 chuck. Here we use dynamic playback in which an automated interaction program counts the number of chucks present in a call and responds according to a specified calling strategy which determines the number of chucks in the response call. Males added progressively more chucks in response to the models' strategies of de-escalate, match or escalate; there was a significant difference in the focal males' responses to the de-escalate versus the escalate strategies. Similarly, males changed their calling strategy in response to the de-escalate strategy of the model. There was no evidence of change in calling patterns, as estimated by entropy, among treatments and between experimental and field data. Males produced significantly more chucks in these experiments than in the field, but in both contexts the mean chuck number is low and never approaches the maximum observed in nature. These data suggest that males are cost-sensitive when it comes to adding chucks and that they are more influenced by vocal competitors that de-escalate rather than escalate number of chucks. These are patterns of calling not previously revealed in studies using static playbacks, and this study is another demonstration of the usefulness of dynamic playback in studies of animal communication.
Reproductive female round gobies (Neogobius melanostomus) are attracted to visual male models at a nest rather than to olfactory stimuli in urine of reproductive males
Authors: Yavno Stan , Corkum Lynda
Published: January 2010

Fish are known to communicate in many ways and commonly use olfactory and visual signals. When round goby (Neogobius melanostomus) males become reproductive, they change from mottled grey to black and release sex steroids in their urine. In this study, we conducted a laboratory experiment to determine if reproductive female round gobies were attracted to a combination of olfactory (urine) and visual (silicone models) stimuli, representing reproductive and non-reproductive male round gobies. Females spent significantly more time at a nest with a black reproductive male model compared with a mottled non-reproductive male model. Neither urine type nor the interaction between model type and urine affected the time spent by reproductive females at a nest. Knowledge of the reproductive habits of the round goby may enable researchers to develop a method of species control for this invasive fish by manipulating its breeding habits.
Reflections on Identity. The Suryoye of the Twelfth and Thirteenth Centuries: Bar Salibi, Bar Shakko, and Barhebraeus
Authors: Teule Herman
Published: January 2010

The present article studies some aspects of the literary output of three Syriac Orthodox authors, Dionysius bar Salibi, Jacob bar Shakko, and Gregory Barhebraeus, who are considered the most important representatives of the period known as 'the Syriac Renaissance' (twelfth and thirteenth centuries). The focus of this study is on the growing importance of Arabic, the concern for the preservation of Syriac, considered as an important identity marker, the influence of Muslim cultural patterns and the West Syrian attitude to Islam as a religious system, and, finally, the emergence or rejection of ideas which tend to consider the Christologies of the East Syrians and Chalcedonians acceptable.
The Copts: 'Modern Sons of the Pharaohs'?
Authors: van der Vliet Jacques
Published: January 2010

This essay briefly reviews the Coptic identity constructions that can be subsumed as 'Pharaonism', and tries to assess them with reference to both ancient sources and modern developments. Broadly speaking, Pharaonism is a way of claiming a deeply rooted national identity that transcends the religious opposition between Egypt's Muslim majority and its indigenous Christian minority, the Copts. As a political ideology it was most successful in the period of the nationwide Egyptian struggle for independence in the early twentieth century, but its impact in particular among Coptic intellectuals is still great. In this essay, it is argued that Pharaonism is shaped in a remarkable degree by western Orientalism, and that its main historical tenets, such as the Copts' indebtedness to pre-Christian, Pharaonic culture or their anti-Greek nationalism, can no longer be maintained.
Supervision and Self-Disclosure: Modes of Supervisory Interaction
Authors: Weinstein Leo S. , Winer Jerome A . , Ornstein Eric
Published: January 2010

A conceptual framework is presented for thinking about supervisory issues raised by candidate self-disclosure. The process of dealing with self-disclosure in supervision brings into bold relief certain dynamics that operate in all supervisory encounters. In responding to these and other tensions stirred by analyst self-disclosure, the supervisory dyad moves in and out of various configurations, or “modes of supervisory interaction.” Why these dynamics are intensified when the focus of supervision is on an instance of candidate self-disclosure is explored. To illustrate these ideas, a supervisory hour that dealt with the issue of self-disclosure is presented. A nonjudgmental awareness of the various modes of supervisory interaction enriches the supervisory process.
Home Bittersweet Home: the Significance of Home for Occupational Transformations
Authors: Lindström Maria , Lindberg Margareta , Sjöström Stefan
Published: January 2010

Background: The study illuminated how persons with psychiatric disabilities experienced the processes of change in a residential context.

Material: Qualitative interviews with residents living in supported housing were conducted and analyzed using constant comparative analysis.

Discussion: Residential conditions appear to provide a complex structure that facilitates rehabilitative interactions, in which ‘progressive tensions’ arise between opposing values, such as authentic versus artificial, and independence versus dependence, both of which are important in the process of change.

Conclusions: A client-centred approach could be taken further if clients are engaged in productive discussions about challenging these ‘progressive tensions’. Awareness of the meaning of home also emerged as central.
Treatment Goals in Addiction Healthcare: the Perspectives of Patients and Clinicians
Authors: Joosten E.A.G. , De Weert-Van Oene G.H. , Sensky T. , Van Der Staak C.P.F. , De Jong C.A.J.
Published: January 2010

Background: Little is known about the perspectives of either patients or clinicians regarding treatment goals in addiction healthcare. In general, treatment goals involve abstinence or at least reduction of substance use.

Aim: To examine and compare the treatment goals indicated by both patients and clinicians at baseline, interim and exit measurement.

Method: A descriptive study was performed with multiple measurements of treatment goals. Patients ( n = 111) and clinicians ( n = 20) were recruited from three addiction treatment centres in the Netherlands. A Shared Decision Making Intervention (SDMI) was undertaken to promote and evaluate treatment agreement.

Results: Patients identified treatment goals of daytime activities and abstinence or reduced alcohol consumption as most important. Clinicians indicated psychological distress, daytime activities and substance use as most important. Differences between patients and clinicians were found for the treatment goals of physical health (patient > clinician) and psychological distress (clinician > patient). The results further showed that treatment goals of both patients and clinicians become more closely aligned during the course of treatment.

Conclusion: SDMI provides a method to explore and discuss discrepancy between patients’ and clinicians’ goals of treatment which leads to convergence. Such convergence is likely to be a necessary prerequisite for positive treatment outcomes.
Towards Social Inclusion Through Lifelong Learning in Mental Health: Analysis of Change in the Lives of the Emilia Project Service Users
Authors: Ramon Shulamit , Griffiths Christopher A. , Nieminen Irja , Pedersen Marialouise , Dawson Ian
Published: January 2010

Background: The application of formal lifelong learning to enhance social inclusion in mental health is rarely investigated in terms of change in the lives of service users on a cross-country comparative scale.

Aims: This study was aimed at examining changes in key areas of the lives of mental health service users across eight European mental health sites.

Method: A before and after case study design was applied. Users of mental health services who participated in the lifelong leaning interventions reviewed the changes in key areas of their lives at baseline and 10 months later, through the thematic analysis of qualitative data collected in semi-structured interviews (27 and 21, respectively) and self-reports (138 and 99, respectively). In-depth examples from one site are provided.

Results: Most users reported positive changes in the areas of training and social networks, with a sizeable minority moving onto unpaid and paid employment. In addition most users reported active planning for job search and other goals. Obstacles that were highlighted included the negative effects of having a mental illness, difficulties in close relationships and economic disadvantages.

Conclusions: The lifelong learning intervention offered within an EU Framework 6 project to mental health service users in eight demonstration sites had a largely positive impact on key areas of their lives at 10 months, though obstacles remained which may be less amenable to change by social interventions.
Are Elderly Dependency Ratios Associated With General Population Suicide Rates?
Authors: Shah Ajit
Published: January 2010

Background: The elderly population size is increasing worldwide due to falling birth rates and increasing life expectancy. It has been hypothesized that as the elderly dependency ratio (the ratio of those over the age of 65 years to those under 65) increases, there will be fewer younger people available to care for older people and this, in turn, will increase the burden on younger carers with increased levels of psychiatric morbidity leading to an increase in general population suicide rates.

Methods: A cross-national study examining the relationship between elderly dependency ratios and general population suicide rates was conducted using data from the World Health Organization and the United Nations websites.

Results: The main findings were of a significant and independent positive correlation between elderly dependency ratios and general population suicide rates in both genders.

Conclusion: The contribution of cross-national differences in psychiatric morbidity in younger carers on general population suicide rates requires further study. The prevalence of psychiatric morbidity in younger carers of older people should be examined by: (i) cross-national studies using standardized measures of psychiatric morbidity that are education-free, culture-fair and language-fair; and (ii) within-country longitudinal studies with changing elderly dependency ratios over time.
Inside the Empire: Ethnography of a Global Citadel in New York
Authors: Smithsimon Gregory
Published: January 2010

For Friedmann and Wolff, the citadel’s physical form—physically defended enclaves in the global city—shapes relations between citadels and outsiders. Subsequent work claims that the designs of citadels produce simulated community life, exclude the city and sanitise public spaces. However, such claims have been based on relatively brief observations. This ethnography assesses the impact of design by examining the quintessential citadel of Battery Park City, in New York City, while the community mobilised against plans for a highway tunnel bordering their community during redevelopment of the neighbouring World Trade Center site. Community life is robust. However, the influence of the physical design is borne out in previously unrecognised ways: residents are identified as a crucial new constituency promoting exclusivity in the global city.
Job Accessibility and Female Employment Probability: The Cases of Barcelona and Madrid
Authors: Matas Anna , Raymond Josep-Lluis , Roig Josep-Lluis
Published: January 2010

The objective of this paper is to estimate the impact of residential job accessibility on female employment probability in the metropolitan areas of Barcelona and Madrid. Following a ‘spatial mismatch’ framework, a female employment probability equation is estimated which includes variables controlling for personal characteristics, residential segregation and employment potential by public transport network. Data used come from the Micro-census 2001 of INE (the National Institute of Statistics). The research focuses on the treatment of endogeneity problems and the measurement of accessibility variables. The results show that low job accessibility in public transport negatively affects employment probability. The intensity of this effect tends to decrease with individual’s educational attainment. A higher degree of residential segregation also reduces job probability in a significant way.
Evolving Reurbanisation? Spatio-temporal Dynamics as Exemplified by the East German City of Leipzig
Authors: Kabisch Nadja , Haase Dagmar , Haase Annegret
Published: January 2010

After a decade of tremendous population loss indicating severe decline, some large east German cities have been displaying signs of reurbanisation since the late 1990s. Using the city of Leipzig as an example, this paper identifies the major characteristics, progress and underlying spatio-temporal dynamics of reurbanisation, and examines whether it is a long-term process of urban living or features only short-term tendencies. Socio-demographic indicators are used to observe the development of inner-city districts. At the spatial scale of municipal districts, time-series data are analysed for the years 1993 to 2005. The paper argues that reurbanisation has occurred primarily in inner-city districts and has progressed considerably since the early 1990s. However, the spatio-temporal distribution of the relevant indicators shows that reurbanisation is far from being a homogeneous process. In light of this, the paper presents a ring of reurbanisation-sensitive municipal districts around the city centre.
Polycentric Regions: Comparing Complementarity and Institutional Governance in the San Francisco Bay Area, the Randstad and Emilia-Romagna
Authors: Cowell Margaret
Published: January 2010

A gap in the literature that remains largely unfilled is a discussion of how polycentrism relates to broader tensions between strategies of specialised industrial agglomeration economies and diverse regional portfolios. Relatively little is known about how strategies of polycentrism relate to the industrial composition and economic complementarity both at the regional scale and for individual cities within the region. In this paper, correspondence analysis is used to quantify complementarity in the economic profiles of cities in three polycentric regions. The findings suggest that the degree of complementarity varies greatly but has decreased in all three of the case study regions over time. Subsequent analysis of institutional structures in these three regions suggests that regions with weaker regional governments, stronger regional identities and intentional polycentric development strategies might experience higher levels of complementarity. A series of hypotheses that relate institutions to complementarity are proposed as possible directions for future research.
The World Bank and the Street: (How) Do ‘Doing Business’ Reforms Affect Tanzania’s Micro-traders?
Authors: Lyons Michal , Titus Msoka Colman
Published: January 2010

The well-documented weaknesses of structural adjustment policies have led to a reconceptualisation of the World Bank’s approach to neo-liberal reforms. The ‘Doing Business’ reforms aim to foster a better climate for business in a number of ways. The main policy documents reject interventions targeted at specific groups but, although they identify informal small and medium enterprises (SMEs) as likely to benefit disproportionately, they specifically exclude micro-enterprises as a target group. The general argument of this paper is that reforms may well impact non-target groups through interactions with several areas of policy and law, with public attitudes and with multiple economic sectors. In particular, it is argued that the exclusion of micro-traders from the reforms contributes to their marginalisation in political and policy arenas, increasing their vulnerability to state intervention. The paper draws on a four-month study conducted by the authors in Tanzania in 2007.
Public Housing and Poverty Concentration in Urban Neighbourhoods: The Case of Hong Kong in the 1990s
Authors: Delang Claudio O. , Ho Cheuk Lung
Published: January 2010

The undesirable effect of public housing on poverty concentration has been recognised by a series of studies that use census-tract-level aggregate data. This paper examines whether the poverty concentration mechanism of public housing that has been observed elsewhere also functions in Hong Kong. Hong Kong has one of the largest supplies of public housing in the world and also a distinct urban environment. After assessing the poverty rates in Hong Kong in 1991 and 2001, we build a series of regression models to examine the impact of public rental housing on poverty concentration during the 1990s. Using aggregated census tract-level data, the analysis concludes that public housing does not necessarily concentrate poverty in particular census tracts. Public policy and city planning by the Hong Kong government are found to be effective in avoiding or reducing the possible adverse effect of public housing by maintaining social heterogeneity and spatial homogeneity.
Self-care Beliefs and Behaviors in Ugandan Adults With Type 2 Diabetes
Authors: Baumann Linda C. , Kenneth Opio Christopher , Otim Marcel , Olson Lindsay , Ellison Shanee
Published: January 2010

Purpose

The purpose of this study was to describe illness beliefs and diabetes self-care behaviors of Ugandan adults with type 2 diabetes.

Methods

A convenience sample of 340 adults with type 2 diabetes was recruited from 2 outpatient settings in Kampala, Uganda. Participants were interviewed by a nurse about diabetes self-care behaviors; had their weight, height, and waist and hip circumference measured; and shared with the interviewer the blood glucose and blood pressure values obtained during their clinic visit.

Results

The majority of participants viewed diabetes as a serious, life-long condition that they had a good deal of control over; however, while 88% believed they could tell high blood glucose by the presence of symptoms, only 39% said they could detect low blood glucose by the presence of symptoms. Self-care challenges include limited access to appropriate food, diabetes medications, blood glucose testing equipment, and educational materials. Subjects reported significant negative psychosocial outcomes associated with having diabetes. Using selected indicators for metabolic syndrome, 87% had elevated blood pressure, and 67% had elevated blood glucose; 33.4% were overweight, and 18.7% were obese.

Conclusions

Results from this study highlight the challenges of diabetes self-care in resource-poor countries. Improving diabetes care will require systems-level interventions to provide access to basic resources as well as to social support and educational interventions.