bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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
Calling strategies of male túngara frogs in response to dynamic playback
Authors: Argo IV  , Goutte  , Kime  , Argo  
Published: January 2010

AbstractTúngara 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

AbstractFish 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

AbstractThe 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

AbstractThis 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.
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.
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.
Bortezomib induces apoptosis in primitive chronic myeloid leukemia cells including LTC-IC and NOD/SCID repopulating cells
Authors: Heaney Nicholas B. , Pellicano Francesca , Zhang Bin , Crawford Lisa , Chu Su , Kazmi Syed M. A. , Allan Elaine K. , Jorgensen Heather G. , Irvine Alexandra E. , Bhatia Ravi , Holyoake Tessa L. 
Published: January 2010

AbstractChronic myeloid leukemia (CML) is treated effectively with tyrosine kinase inhibitors (TKIs); however, 2 key problems remain—the insensitivity of CML stem and progenitor cells to TKIs and the emergence of TKI-resistant BCR-ABL mutations. BCR-ABL activity is associated with increased proteasome activity and proteasome inhibitors (PIs) are cytotoxic against CML cell lines. We demonstrate that bortezomib is antiproliferative and induces apoptosis in chronic phase (CP) CD34+ CML cells at clinically achievable concentrations. We also show that bortezomib targets primitive CML cells, with effects on CD34+38−, long-term culture-initiating (LTC-IC) and nonobese diabetic/severe combined immunodeficient (NOD/SCID) repopulating cells. Bortezomib is not selective for CML cells and induces apoptosis in normal CD34+38− cells. The effects against CML cells are seen when bortezomib is used alone and in combination with dasatinib. Bortezomib causes proteasome but not BCR-ABL inhibition and is also effective in inhibiting proteasome activity and inducing apoptosis in cell lines expressing BCR-ABL mutations, including T315I. By targeting both TKI-insensitive stem and progenitor cells and TKI-resistant BCR-ABL mutations, we believe that bortezomib offers a potential therapeutic option in CML. Because of known toxicities, including myelosuppression, the likely initial clinical application of bortezomib in CML would be in resistant and advanced disease.