bluuebunny/crossref_metadata_2025 huggingface dataset:
BRAF Inhibitor Vemurafenib Improves the Antitumor Activity of Adoptive Cell Immunotherapy
Authors: Koya Richard C. , Mok Stephen , Otte Nicholas , Blacketor Kevin J. , Comin-Anduix Begonya , Tumeh Paul C. , Minasyan Aspram , Graham Nicholas A. , Graeber Thomas G. , Chodon Thinle , Ribas Antoni
Published: June 2012

Combining immunotherapy with targeted therapy blocking oncogenic BRAFV600 may result in improved treatments for advanced melanoma. In this study, we developed a BRAFV600E-driven murine model of melanoma, SM1, which is syngeneic to fully immunocompetent mice. SM1 cells exposed to the BRAF inhibitor vemurafenib (PLX4032) showed partial in vitro and in vivo sensitivity resulting from the inhibition of MAPK pathway signaling. Combined treatment of vemurafenib plus adoptive cell transfer therapy with lymphocytes genetically modified with a T-cell receptor (TCR) recognizing chicken ovalbumin (OVA) expressed by SM1-OVA tumors or pmel-1 TCR transgenic lymphocytes recognizing gp100 endogenously expressed by SM1 resulted in superior antitumor responses compared with either therapy alone. T-cell analysis showed that vemurafenib did not significantly alter the expansion, distribution, or tumor accumulation of the adoptively transferred cells. However, vemurafenib paradoxically increased mitogen-activated protein kinase (MAPK) signaling, in vivo cytotoxic activity, and intratumoral cytokine secretion by adoptively transferred cells. Taken together, our findings, derived from 2 independent models combining BRAF-targeted therapy with immunotherapy, support the testing of this therapeutic combination in patients with BRAFV600 mutant metastatic melanoma. Cancer Res; 72(16); 3928–37. ©2012 AACR.
VEGF Exerts an Angiogenesis-Independent Function in Cancer Cells to Promote Their Malignant Progression
Authors: Cao Ying , E Guangqi , Wang Enfeng , Pal Krishnendu , Dutta Shamit K. , Bar-Sagi Dafna , Mukhopadhyay Debabrata
Published: June 2012

VEGF/vascular permeability factor (VEGF/VPF or VEGF-A) is a pivotal driver of cancer angiogenesis that is a central therapeutic target in the treatment of malignancy. However, little work has been devoted to investigating functions of VEGF that are independent of its proangiogenic activity. Here, we report that VEGF produced by tumor cells acts in an autocrine manner to promote cell growth through interaction with the VEGF receptor neuropilin-1 (NRP-1). Reducing VEGF expression by tumor cells induced a differentiated phenotype in vitro and inhibited tumor forming capacity in vivo, independent of effects on angiogenesis. Autocrine activation of tumor cell growth was dependent on signaling through NRP-1, and Ras was determined to be a critical effector signaling molecule downstream of NRP-1. Our findings define a novel function for VEGF in dedifferentiation of tumor cells expanding its role in cancer beyond its known proangiogenic function. Cancer Res; 72(16); 3912–8. ©2012 AACR.
Outcomes After Unrestricted Use of Everolimus-Eluting and Sirolimus-Eluting Stents in Routine Clinical Practice
Authors: Park Duk-Woo , Kim Young-Hak , Song Hae-Geun , Ahn Jung-Min , Kim Won-Jang , Lee Jong-Young , Kang Soo-Jin , Lee Seung-Whan , Lee Cheol Whan , Park Seong-Wook , Yun Sung-Cheol , Her Sung Ho , Hur Seung Ho , Park Jin Sik , Kim Myeong-Kon , Choi Yun Seok , Kim Hyun Sook , Cho Jang-Hyun , Lee Sang Gon , Park Yong Whi , Jeong Myung-Ho , Lee Bong Ki , Lee Nae-Hee , Lim Do-Sun , Yoon Junghan , Seung Ki Bae , Shin Won-Yong , Rha Seung-Woon , Kim Kee-Sik , Tahk Seung-Jea , Park Byoung Eun , Ahn Taehoon , Yang Joo-Young , Jeong Yong Seok , Rhew Jay-Hyun , Park Seung-Jung
Published: June 2012

Background—

It remains unclear whether there are differences in the safety and efficacy outcomes between everolimus-eluting stents (EES) and sirolimus-eluting stents (SES) in contemporary practice.

Methods and Results—

We prospectively enrolled 6166 consecutive patients who received EES (3081 patients) and SES (3085 patients) between April 2008 and June 2010, using data from the Interventional Cardiology Research In-Cooperation Society-Drug-Eluting Stents Registry. The primary end point was a composite of death, nonfatal myocardial infarction (MI), or target-vessel revascularization (TVR). At 2 years of follow-up, the 2 study groups did not differ significantly in crude risk of the primary end point (12.1% for EES versus 12.4% for SES; HR, 0.97; 95% CI, 0.84–1.12,
P
=0.66). After adjustment for differences in baseline risk factors, the adjusted risk for the primary end point remained similar for the 2 stent types (HR, 0.96; 95% CI, 0.82–1.12,
P
=0.60). There were also no differences between the stent groups in the adjusted risks of the individual component of death (HR, 0.93; 95% CI, 0.67–1.30,
P
=0.68), MI (HR, 0.97; 95% CI, 0.79–1.18,
P
=0.74), and TVR (HR, 1.10; 95% CI, 0.82–1.49,
P
=0.51). The adjusted risk of stent thrombosis also was similar (HR, 1.16; 95% CI, 0.47–2.84,
P
=0.75).

Conclusions—

In contemporary practice of percutaneous coronary intervention procedures, the unrestricted use of EES and SES showed similar rates of safety and efficacy outcomes with regard to death, MI, sent thrombosis, and TVR. Future longer-term follow-up is needed to better define the relative benefits of these drug-eluting stents.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01070420.
Ethiopia’s social protection landscape: Its surface and underlying structures
Authors: Hailu Daniel , Northcut Terry
Published: June 2012

This article demonstrates the utility of explicating underlying forces that have brought about, shaped and underpinned provision of social protection in each sub-Saharan African country. It does so in the context of examining six such forces, namely: tradition and culture, drought and famine, relations among key actors, the mainstream paradigm of development, the poverty reduction agenda of the ruling party, and constrained fiscal space that have historically contributed to current provision of social protection in Ethiopia. Recommendations are given for social work policy practice to enable decision-makers to integrate developmental and human rights objectives in Ethiopia’s forthcoming national social protection strategy.
Examination of Hashin’s failure criteria for the second world-wide failure exercise
Authors: Kress G
Published: June 2012

The second world-wide failure exercise is an international activity, organised by Kaddour and Hinton, aiming at a better understanding of the limitations of existing failure criteria to predict failure under triaxial stressing. The present work is a response to an invitation to take part and employ Hashin's failure criteria to the 12 test cases defined by the organizers of the second world-wide failure exercise. Methods, based on nonlinear analysis, used to perform the required simulations are explained and the predictions are presented. Observed problems are discussed.
Which Are the Real Determinants of Tenure? A Comparative Analysis of Different Models of the Tenure Choice of a House
Authors: Raya Josep , Garcia Jaume
Published: June 2012

Tenure choice is closely bound to other vital individual decisions of great importance not only for the individual but also for the country in which he or she resides. The present paper includes a comparison of the different approaches that have been used in the economic literature in the analysis of the individual’s housing tenure choice. According to their dependent variable, the different models can be divided into: those whose dependent variable is tenure (classical models, ‘recent movers’ models and sequential models) and those in which the dependent variable is transition from renting to the position of ownership (duration models and ‘choice-based’ models). Results show the best performance for the models in which the variable to be explained is the transition from renting to ownership and highlight real determinants of tenure (life-cycle variables) and transition (life-cycle variables, prices and transaction costs). Finally, marital status stands out as the variable with the highest incidence.
Five Ethical Paradigms for Community College Leaders
Authors: Wood J. Luke , Hilton Adriel A.
Published: June 2012

This article encourages community college leaders to employ ethical paradigms when constructing and considering alternative courses of action in decision-making processes. The authors discuss four previously articulated paradigms (e.g., ethic of justice, ethic of critique, ethic of care, and ethic of the profession) and propose an additional paradigm—the ethic of local community. The ethic of local community is a communitarian and utilitarian frame embodied by the philosophical underpinnings and mission of the community college. Questions designed for praxis are proffered following a discourse on how each paradigm is defined and described in extant literature.
Hiring Diverse Faculty Members in Community Colleges
Authors: Fujimoto Eugene Oropeza
Published: June 2012

This case study examines why 2-year colleges struggle to increase the racial diversity of their faculty. Through interrogating hiring procedures and identifying reasonable expectations for diversity within a college faculty, ethical dilemmas and practical implications of efforts to increase the hiring of faculty members of color emerge.
Recent policy changes in the Universal Child Benefit in Japan
Authors: Tokoro Michihiko
Published: June 2012

Japan is rapidly aging, due to longer life expectancy and fewer children. Japanese social policy has tried to reduce the impacts of demographic changes by providing social services and benefits. The dominant Democratic Party of Japan came into power in the 2009 election after promising to extend child benefit, and following its landslide victory, the DPJ-led Government introduced the first universal child benefit in Japanese history. But barely more than two years on, the Government has been forced to abolish the benefit by a combination of strong opposition and financial crisis. This article will summarise the details of this child benefit controversy and look into the real problems of the Japanese welfare system behind the issues.
Follow the verbs! A contribution to the study of the Heidegger–Latour connection
Authors: Schiølin Kasper
Published: June 2012

Recently, various scholars have attempted to combine the philosophies of Martin Heidegger and Bruno Latour, despite seeming contrasts between them. The present study adds a new perspective to the opening up of this theoretical borderland. In this article, I show how Heidegger’s dispute with the philosophical tradition’s essentialistic and substantialistic treatment of being, and Latour’s dispute with sociology’s hypostatisation of the social, share the expression of an epistemological battle against substances, which is most evident in both of their attempts to include technology and things in their thought. Substances are mostly expressed in nouns. Because of this, Heidegger’s and Latour’s disputes have a grammatical dimension, which in different ways aims to emphasise verbs rather than the nouns in their respective terminology. This grammatical dimension of their shared dispute with substantialism will be demonstrated in this article. I conclude by arguing that Latour’s a famous methodological injunction, ‘Follow the actors!’ can be rewritten as ‘Follow the verbs!’.
Proactive Motor Control Reduces Monetary Risk Taking in Gambling
Authors: Verbruggen Frederick , Adams Rachel , Chambers Christopher D.
Published: June 2012

Less supervision by the executive system after disruption of the right prefrontal cortex leads to increased risk taking in gambling because superficially attractive—but risky—choices are not suppressed. Similarly, people might gamble more in multitask situations than in single-task situations because concurrent executive processes usually interfere with each other. In the study reported here, we used a novel monetary decision-making paradigm to investigate whether multitasking could reduce rather than increase risk taking in gambling. We found that performing a task that induced cautious motor responding reduced gambling in a multitask situation (Experiment 1). We then found that a short period of inhibitory training lessened risk taking in gambling at least 2 hr later (Experiments 2 and 3). Our findings indicate that proactive motor control strongly affects monetary risk taking in gambling. The link between control systems at different cognitive levels might be exploited to develop new methods for rehabilitation of addiction and impulse-control disorders.
The relationship of ethics education to moral sensitivity and moral reasoning skills of nursing students
Authors: Park Mihyun , Kjervik Diane , Crandell Jamie , Oermann Marilyn H
Published: June 2012

This study described the relationships between academic class and student moral sensitivity and reasoning and between curriculum design components for ethics education and student moral sensitivity and reasoning. The data were collected from freshman ( n = 506) and senior students ( n = 440) in eight baccalaureate nursing programs in South Korea by survey; the survey consisted of the Korean Moral Sensitivity Questionnaire and the Korean Defining Issues Test. The results showed that moral sensitivity scores in patient-oriented care and conflict were higher in senior students than in freshman students. Furthermore, more hours of ethics content were associated with higher principled thinking scores of senior students. Nursing education in South Korea may have an impact on developing student moral sensitivity. Planned ethics content in nursing curricula is necessary to improve moral sensitivity and moral reasoning of students.
Being different and suffering the consequences: The influence of head coach–player racial dissimilarity on experienced incivility
Authors: Cunningham George B , Miner Kathi , McDonald Jennifer
Published: June 2012

The purpose of the current study was to examine how head coach–player racial dissimilarity was associated with negative treatment from the head coach. Data were collected from 212 National Collegiate Athletic Association (NCAA) Division I women’s basketball players (124 Whites, 88 African Americans). Results indicate that racial dissimilarity was associated with greater incivility when the head coach was White, but not when the head coach was African American. In addition, incivility was negatively associated with players’ commitment to the team. The authors discuss theoretical contributions and practical implications.
Cross-Ethnicity Measurement Equivalence of Family Coping for Breast Cancer Survivors
Authors: Lim Jung-won , Townsend Aloen
Published: June 2012

Objective: The current study examines the equivalence of a measure of family coping, the Family Crisis Oriented Personal Evaluation scales (F-COPES), in Chinese American and Korean American breast cancer survivors (BCS). Methods: Factor structure and cross-ethnicity equivalence of the F-COPES were tested using structural equation modeling with 157 Chinese American and Korean American BCS in California. Results: Of the original F-COPES subscales, acquiring social support, reframing, and passive appraisal did not adequately fit the data. Thus, a modified five-factor structure of the F-COPES was created. The modified F-COPES was validated with respect to quality of life, psychological distress, and family communication. Conclusions: The findings illustrate the importance of cross-ethnicity measurement testing and provide a rationale for developing culturally tailored measurements for ethnic minority populations.
Factor Structure of the Chinese Virtues Questionnaire
Authors: Duan Wenjie , Ho Samuel M. Y. , Yu Bai , Tang Xiaoqing , Zhang Yonghong , Li Tingting , Yuen Tom
Published: June 2012

Objectives: The present study examined the factorial invariance and functional equivalence of the Values in Action Inventory of Strengths (VIA-IS) among the Chinese. Methods: A total of 839 undergraduate students completed the 240-item Simplified Chinese version of the VIA-IS online. Another 40 students participated in qualitative interviews to examine the meaning and function of the items in Chinese culture. Results: A total of 144 items were removed from the original version questionnaire (240-item) because of low item-loading and lack of cultural validity. A Chinese Virtues Questionnaire-96 (CVQ-96) in simplified Chinese containing 96 items (4 items per strength) was adopted. Three subscales (interpersonal, vitality, and cautiousness) were developed after exploratory factor analysis and confirmatory factor analysis. Conclusion: A theoretically meaningful 3-factor model of virtue, comparable to some virtue structures proposed in previous studies conducted in Western countries, was obtained. The inventories being developed can facilitate positive social work assessment and intervention.
Coordination Costs for School-Located Influenza Vaccination Clinics, Maine, 2009 H1N1 Pandemic
Authors: Asay Garrett R. Beeler , Cho Bo-Hyun , Lorick Suchita A. , Tipton Meredith L. , Dube Nancy L. , Messonnier Mark L.
Published: June 2012

School nurses played a key role in Maine’s school-located influenza vaccination (SLV) clinics during the 2009–2010 pandemic season. The objective of this study was to determine, from the school district perspective, the labor hours and costs associated with outside-clinic coordination activities (OCA). The authors defined OCA as labor hours spent by staff outside of clinic operations. The authors surveyed a convenience sample of 10 school nurses from nine school districts. Eight nurses responded to the survey, representing seven districts, 45 schools and 84 SLV clinics that provided a total of 22,596 vaccine doses (H1N1 and seasonal combined) to children and adolescents. The mean total OCA time per clinic was 69 hours: out of total hours, 22 (36%) were spent outside regular clinic operation time. The authors estimated the mean cost of OCA to be $15.36 per dose. Survey respondents reported that costs would be lower during non-pandemic seasons and as schools become more proficient at planning clinics.
The Indirect Effects of Auditing Taxpayers
Authors: Ratto Marisa , Thomas Richard , Ulph David
Published: June 2012

Empirical studies suggest that the effects of tax audits are not only in terms of recovered unpaid tax (direct effect) but there are also indirect effects in terms of future better compliance that tend to outweigh the direct effect. However, current policy decisions on the allocation of investigation resources across different groups of taxpayers generally neglect the indirect effects, generating a potential resource misallocation issue. With the aim to clarify a possible mechanism through which the indirect effects work, the authors model tax compliance as a social norm and show that taxpayers’ interdependencies introduce a multiplier effect to an increase in the audit rate.
Beyond armed camps: A response to Stokoe
Authors: Silverman David
Published: June 2012

In this response, I examine the ambiguity about the status of Membership Categorization Device Analysis (MCDA) in the work of Harvey Sacks. The ‘five guiding principles’ of MCDA that Stokoe enunciates serve as a crucial guide to future research. In what follows, I give some further examples of data analysis which, I believe, supports both her strong and weaker claims.
Membership categorization analysis: Wild and promiscuous or simply the joy of Sacks?
Authors: Fitzgerald Richard
Published: June 2012

The recent resurgence of Sacks’ work on membership categorization has highlighted the growing analytic interest in how members’ social category orientations operate at multiple levels of interactional work. One of the outcomes of this, highlighted in Stokoe’s discussion, is the re-emergence of the question of whether membership categorization analysis (MCA) has been, is, or can be an approach in its own right. In this brief discussion I consider the emergence of ‘MCA’ as an approach to the study of social-knowledge-in-action, the relationship between MCA and contemporary directions in conversation analysis (CA), and finally the future of MCA as it continues to develop.
Maybe I Can Learn to Read in College
Authors: Head-Dylla Candace
Published: June 2012

Can poor student performance on high-stakes assessment, including high school exit exams, indicate gaps in school and district curriculum and instruction? How might this affect students identified with special needs, and what could it mean in terms of a free and appropriate public education? This case illustrates how a student receiving special education services progressed in a school system with accommodations and modifications, only to fall short on a high-stakes exam at the end of his school career. The study explores what challenges this poses for the individual student as well as the entire school system and its leaders.
Policy, Power, and Predicaments
Authors: Dolder-Holland Tiffany , Whiteman Rodney S. , Fetter-Harrott Alli
Published: June 2012

Joe McGinnis, principal of Jackson High School, is caught in the conflict between community values, parents’ rights, teacher speech, public health policy, and his own positioning within the community and faculty. He must decide whether and how to discipline a teacher and former mentor who, in the absence of a clear school district policy, supplied a student with information regarding sexual health. The parents claim the teacher exceeded her duties by providing morality education that contradicted parental and community values. The teacher asserts she acted in the best interest of the student’s health and academic future. This case poses questions about professional ethics and morality, community governance and school health education policies, school human resource rules, and school power.
Establishing HIV treatment as prevention in the HIV Prevention Trials Network 052 randomized trial: an ethical odyssey
Authors: Cohen Myron S , McCauley Marybeth , Sugarman Jeremy
Published: June 2012

Background Obtaining the definitive data necessary to determine the safety and efficacy of using antiretroviral treatment (ART) to reduce the sexual transmission of HIV in heterosexual couples encountered an array of ethical challenges that threatened to compromise HIV Prevention Trials Network (HPTN) 052, the multinational clinical trial addressing this issue that has profound public health implications.

Purpose To describe and analyze the major ethical challenges faced in HPTN 052.

Methods The ethical issues and modifications of HPTN 052 in response to these issues were cataloged by the principal investigator, the lead coordinator, and the ethicist working on the trial. The major ethical issues that were unique to the trial were then described and analyzed in light of the published literature as well as guidances and policies. The ethical challenges that must be addressed in many clinical trials, such as those related to obtaining informed consent and making provisions for ancillary care, are not described.

Results When HPTN 052 was being designed, ethical questions emerged related to the relevance of the research question itself given data from observational research and a range of beliefs about the appropriate means of preventing and treating HIV infection and AIDS. Furthermore, ethical challenges were faced regarding site selection since there was a scientific need to conduct the research in settings where HIV incidence was high, but alternatives to study participation should be available. As in most HIV-prevention research, ethical questions surrounded the determination of the appropriate prevention package for all of those enrolled. During the course of the trial, guidance documents and policies emerged that were of direct relevance to the research questions, calling for a balancing of concerns for the research subjects and trial integrity. When the study results were made public, there was a need to ensure access to the treatment shown to be effective that in some cases differed from the guidelines used at the sites where the research was being conducted. In addition, questions were raised about whether there was an obligation to notify subjects about ‘unlinked’ transmissions of HIV, that is, infections acquired from someone other than the designated sexual partner enrolled in the study.

Limitations The ethical issues described are limited to those discerned by the authors and not those of other stakeholders who may have identified additional issues or had a different perspective in analyzing them.

Conclusions Understanding the ethical challenges faced in HPTN 052 promises to inform the design and conduct of future complex, long-term clinical trials aimed at addressing critical scientific and public health questions, where data and practice patterns emerge over the course of the trial.
The Case against Ethics Review in the Social Sciences
Authors: Schrag Zachary M.
Published: June 2012

For decades, scholars in the social sciences and humanities have questioned the appropriateness and utility of prior review of their research by human subjects' ethics committees. This essay seeks to organize thematically some of their published complaints and to serve as a brief restatement of the major critiques of ethics review. In particular, it argues that 1) ethics committees impose silly restrictions, 2) ethics review is a solution in search of a problem, 3) ethics committees lack expertise, 4) ethics committees apply inappropriate principles, 5) ethics review harms the innocent, and 6) better options exist.
Protecting Research Subjects from Prohibited Multi-Participation in Clinical Trials
Authors: Graf Hans-Peter
Published: June 2012

The protection of human research subjects in clinical studies is regulated by international guidelines and national laws. Research Ethics Committees play an important role here, as they review the documentation for clinical studies under consideration of ethical aspects. This documentation includes an exclusion or wash-out period which designates when study subjects may not have participated in another study or be allowed to take part in a future one within a specified time period. However not all research subjects comply with their applicable exclusion period. This prohibited multi-participation in clinical studies is known as ‘research subject tourism,’ ‘clinical study overlapping’, or ‘guinea-pigging’. This practice brings with it additional risks for the research subject and the integrity of the research being conducted. No comprehensive data are available to demonstrate exactly how many research subjects participate in overlapping multiple studies. However, the number of them who ‘travel’ from one study to another seems to be significant. Preventing this practice is a matter of concern for ethics committees, but the responsibility for protecting research subjects in this respect apart from approving the ethics of a wash-out period and recruiting from a specific pool or database of patients is solely that of the investigating physician. But how can the investigating physician be certain that a research subject complies with their exclusion period? An international data bank for research subjects who have participated, or are participating, in clinical studies, is a measure that would serve to prevent prohibited multi-participation in clinical studies and thereby protect the research subject, the investigating physician and their institution. VIP Check, International, which was founded by the author in 1990, is an example of such a data bank.

This article examines the existence of prohibited multi-participation in clinical studies, the additional risk this practice of itself poses to the research subjects and the integrity of clinical studies, and how this practice might best be reduce or even eliminated through use of an international data bank of research subjects such as that of VIP Check.
‘Hand of God’, Shirt of the Man: The Materiality of Diego Maradona
Authors: Hughson John , Moore Kevin
Published: June 2012

Among the ‘first eleven’ items of interest in the National Football Museum, Manchester, UK is the football shirt worn by Diego Maradona (b. 1960) in the 1986 FIFA World Cup quarter-final match between Argentina and England. This paper reflects upon the cultural significance of the shirt as a museum object. A discussion of the shirt’s history, from its wearing at the 1986 match to its imminent reappearance in the National Football Museum’s new location, leads to the conclusion that, above all, although it may be subject to differing symbolic interpretations, the shirt exists as a material object, the observation of which affords football aesthetes an appreciative reminder of Maradona’s extraordinary artistry with a ball at his feet.
Aquadynamics and the Athletocracy: Jennie Fletcher and the British Women’s 4×100 metre Freestyle Relay Team at the 1912 Stockholm Olympic Games
Authors: Williams Jean
Published: June 2012

This article considers the part played by aquadynamics, or a concern for the technical properties of swimming costumes, in the career of Jennie Fletcher (1890–1968) who won Britain’s first individual Olympic female swimming medal (bronze) at the Stockholm Olympic Games in 1912 and contributed to the first women’s team gold in the 4×100 metre Freestyle Relay. Her light silk one-piece racing swimsuit represented a new kind of modernity: the revealed sporting body enabled competitive principles, rather than modesty, to define the appearance of the female swimmer. The article also examines the place of the working-class competitor in our understanding of the early Games, an ‘athletocracy’ where performance, not background, enabled individuals to compete. The work therefore also explores the relevance of Fletcher’s birthplace, Leicester, in the development of amateur and professional swimming and in the production of swmming costumes for both sport and leisure.
Fourier transform infrared spectroscopy study of acid birnessites before and after Pb2+ adsorption
Authors: Zhao Wei , Liu Fan , Feng Xionghan , Tan Wenfeng , Qiu Guohong , Chen Xiuhua
Published: June 2012

To provide fundamental knowledge for studying the relative content of vacant sites and exploring the mechanism of interaction between Pb2+ and birnessite, Fourier transform infrared spectroscopy (FTIR) of birnessites with different Mn average oxidation states (AOS) before and after Pb2+ adsorption were investigated. The number of absorption bands of FTIR spectra was determined by using the second derivatives of the original spectra. The band at 899–920 cm–1 was assigned to the bending vibration of -OH located at vacancies. The bands at 1059–1070, 1115–1124 and 1165–1171 cm–1 could be attributed to the vibrations of Mn(III)-OH in MnO6 layers, and the intensities of these bands increased with decreasing Mn AOS. The bands at 990 and 1023–1027 cm–1 were ascribed to the vibrations of Mn(III)-OH in the interlayers. Mn(III) in MnO6 layers partially migrated to interlayers during Pb2+ adsorption, which led to an increased intensity of the band at 990 cm–1. The band at 564–567cm–1 was assigned to the vibration of Mn-O located at vacancies. This band could split by coupling of vibrations due to Pb2+ and/or Mn2+ adsorbed at vacant sites. The large distance between the band at 610–626 cm–1 and that at 638–659 cm–1 might reflect small Mn(III) ions located in Mn(III)-rich rows.
Vav3 collaborates with p190-BCR-ABL in lymphoid progenitor leukemogenesis, proliferation, and survival
Authors: Chang Kyung Hee , Sanchez-Aguilera Abel , Shen Shuhong , Sengupta Amitava , Madhu Malav N. , Ficker Ashley M. , Dunn Susan K. , Kuenzi Ashley M. , Arnett Jorden L. , Santho Rebecca A. , Agirre Xabier , Perentesis John P. , Deininger Michael W. , Zheng Yi , Bustelo Xose R. , Williams David A. , Cancelas Jose A.
Published: June 2012

Despite the introduction of tyrosine kinase inhibitor therapy, the prognosis for p190-BCR-ABL+ acute lymphoblastic leukemia remains poor. In the present study, we present the cellular and molecular roles of the Rho GTPase guanine nucleotide exchange factor Vav in lymphoid leukemogenesis and explore the roles of Vav proteins in BCR-ABL–dependent signaling. We show that genetic deficiency of the guanine nucleotide exchange factor Vav3 delays leukemogenesis by p190-BCR-ABL and phenocopies the effect of Rac2 deficiency, a downstream effector of Vav3. Compensatory up-regulation of expression and activation of Vav3 in Vav1/Vav2–deficient B-cell progenitors increases the transformation ability of p190-BCR-ABL. Vav3 deficiency induces apoptosis of murine and human leukemic lymphoid progenitors, decreases the activation of Rho GTPase family members and p21-activated kinase, and is associated with increased Bad phosphorylation and up-regulation of Bax, Bak, and Bik. Finally, Vav3 activation only partly depends on ABL TK activity, and Vav3 deficiency collaborates with tyrosine kinase inhibitors to inhibit CrkL activation and impair leukemogenesis in vitro and in vivo. We conclude that Vav3 represents a novel specific molecular leukemic effector for multitarget therapy in p190-BCR-ABL–expressng acute lymphoblastic leukemia.
Regulatory dendritic cells program B cells to differentiate into CD19hiFcγIIbhi regulatory B cells through IFN-β and CD40L
Authors: Qian Li , Qian Cheng , Chen Yongjian , Bai Yi , Bao Yan , Lu Liwei , Cao Xuetao
Published: June 2012

Regulatory dendritic cells (DCs) play important roles in the induction of peripheral tolerance and control of adaptive immune response. Our previous studies demonstrate that splenic stroma can drive mature DCs to proliferate and further differentiate into a unique subset of CD11bhiIalow regulatory DCs, which could inhibit T-cell response, program generation of immunosuppressive memory CD4 T cells. However, the effect of regulatory DCs on B-cell function remains unclear. Here, we report that regulatory DCs can induce splenic B cells to differentiate into a distinct subtype of IL-10–producing regulatory B cells with unique phenotype CD19hiFcγIIbhi. CD19hiFcγIIbhi B cells inhibit CD4 T-cell response via IL-10. CD19hiFcγIIbhi B cells have enhanced phagocytic capacity compared with conventional CD19+ B cells, and FcγRIIb mediates the uptake of immune complex by CD19hiFcγIIbhi B cells. We found that regulatory DC-derived IFN-β and CD40 ligand are responsible for the differentiation of CD19hiFcγIIbhi B cells. Furthermore, an in vivo counterpart of CD19hiFcγIIbhi B cells in the spleen and lymph nodes with similar phenotype and regulatory function has been identified. Our results demonstrate a new manner for regulatory DCs to down-regulate immune response by, at least partially, programming B cells into regulatory B cells.
Probing the Xenopus laevis inner ear transcriptome for biological function
Authors: Powers TuShun R , Virk Selene M , Trujillo-Provencio Casilda , Serrano Elba E
Published: June 2012

Background

The senses of hearing and balance depend upon mechanoreception, a process that originates in the inner ear and shares features across species. Amphibians have been widely used for physiological studies of mechanotransduction by sensory hair cells. In contrast, much less is known of the genetic basis of auditory and vestibular function in this class of animals. Among amphibians, the genus Xenopus is a well-characterized genetic and developmental model that offers unique opportunities for inner ear research because of the amphibian capacity for tissue and organ regeneration. For these reasons, we implemented a functional genomics approach as a means to undertake a large-scale analysis of the Xenopus laevis inner ear transcriptome through microarray analysis.

Results

Microarray analysis uncovered genes within the X. laevis inner ear transcriptome associated with inner ear function and impairment in other organisms, thereby supporting the inclusion of Xenopus in cross-species genetic studies of the inner ear. The use of gene categories (inner ear tissue; deafness; ion channels; ion transporters; transcription factors) facilitated the assignment of functional significance to probe set identifiers. We enhanced the biological relevance of our microarray data by using a variety of curation approaches to increase the annotation of the Affymetrix GeneChip® Xenopus laevis Genome array. In addition, annotation analysis revealed the prevalence of inner ear transcripts represented by probe set identifiers that lack functional characterization.

Conclusions

We identified an abundance of targets for genetic analysis of auditory and vestibular function. The orthologues to human genes with known inner ear function and the highly expressed transcripts that lack annotation are particularly interesting candidates for future analyses. We used informatics approaches to impart biologically relevant information to the Xenopus inner ear transcriptome, thereby addressing the impediment imposed by insufficient gene annotation. These findings heighten the relevance of Xenopus as a model organism for genetic investigations of inner ear organogenesis, morphogenesis, and regeneration.
An important role of interleukin-10 in counteracting excessive immune response in HT-29 cells exposed to Clostridium butyricum
Authors: Gao Quanxin , Qi Lili , Wu Tianxing , Wang Jinbo
Published: June 2012

Background

Clostridium butyricumhas become increasingly important in preventing and treating intestinal inflammation. In the intestine it may increase the resistance of the gut to pathogen invasion via inducing the secretion of anti-inflammatory cytokines. Interleukin 10 (IL-10) plays a central role in preventing certain inflammatory diseases by down-regulating inflammatory cascades. In a previous study, we observed that the level of IL-10 mRNA was modulated byC. butyricum. The aim of this study was to investigate whetherC. butyricumachieves its beneficial effects through IL-10.

Results

We treated HT-29 cells with anti-IL-10 (IL-10 antibody) or siIL-10 (IL-10 small interfering RNA) to disrupt IL-10. In both cases, the effects ofC. butyricum-induced NF-κB activation and IL-8 expression were enhanced. We also found that neutralization or knockdown of IL-10 could induce apoptosis and necrosis of HT-29 cells treated withC. butyricumcompared with control cells.

Conclusions

These findings show that IL-10 serves an important role inC. butyricum-mediated immune protection, and in host recognition ofC. butyricum.
Mycobacterium fortuitum as a cause of peritoneal dialysis-associated peritonitis: case report and review of the literature
Authors: Jiang Simon H , Roberts Darren M , Dawson Andrew H , Jardine Meg
Published: June 2012

Background

Peritoneal dialysis-associated peritonitis (PD-peritonitis) due to Mycobacterium spp is uncommon. Non-tuberculous Mycobacterium (NTB) PD-peritonitis can present in a similar fashion to more common causes of bacterial PD-peritonitis. We describe the first reported case of multiresistant Mycobacterium fortuitum PD-peritonitis in an Australian patient.

Case presentation

A 38 year-old woman developed mild PD-peritonitis during an overseas holiday. Treatment was complicated by delayed diagnosis, requirement for special investigations, treatment with multiple antibiotics, and conversion to haemodialysis following removal of her Tenckhoff catheter.

Conclusion

This case demonstrates the diagnostic yield of pursuing further investigations in cases of initially culture-negative, problematic PD-peritonitis. A systematic review of the literature identified only 17 reports of M. fortuitum PD-peritonitis. Similar to our case, a delay in microbiological diagnosis was frequently noted and the Tenckhoff catheter was commonly removed at the time of diagnosis. The type and duration of antibiotic therapy also varied widely so the optimum treatment appears to be poorly defined.
ERLIN2 promotes breast cancer cell survival by modulating endoplasmic reticulum stress pathways
Authors: Wang Guohui , Liu Gang , Wang Xiaogang , Sethi Seema , Ali-Fehmi Rouba , Abrams Judith , Zheng Ze , Zhang Kezhong , Ethier Stephen , Yang Zeng-Quan
Published: June 2012

Background

Amplification of the 8p11-12 region has been found in approximately 15% of human breast cancer and is associated with poor prognosis. Previous genomic analysis has led us to identify the endoplasmic reticulum (ER) lipid raft-associated 2 (ERLIN2) gene as one of the candidate oncogenes within the 8p11-12 amplicon in human breast cancer, particularly in the luminal subtype. ERLIN2, an ER membrane protein, has recently been identified as a novel mediator of ER-associated degradation. Yet, the biological roles of ERLIN2 and molecular mechanisms by which ERLIN2 coordinates ER pathways in breast carcinogenesis remain unclear.

Methods

We established the MCF10A-ERLIN2 cell line, which stably over expresses ERLIN2 in human nontransformed mammary epithelial cells (MCF10A) using the pLenti6/V5-ERLIN2 construct. ERLIN2 over expressing cells and their respective parental cell lines were assayed for in vitro transforming phenotypes. Next, we knocked down the ERLIN2 as well as the ER stress sensor IRE1α activity in the breast cancer cell lines to characterize the biological roles and molecular basis of the ERLIN2 in carcinogenesis. Finally, immunohistochemical staining was performed to detect ERLIN2 expression in normal and cancerous human breast tissues

Results

We found that amplification of the ERLIN2 gene and over expression of the ERLIN2 protein occurs in both luminal and Her2 subtypes of breast cancer. Gain- and loss-of-function approaches demonstrated that ERLIN2 is a novel oncogenic factor associated with the ER stress response pathway. The IRE1α/XBP1 axis in the ER stress pathway modulated expression of ERLIN2 protein levels in breast cancer cells. We also showed that over expression of ERLIN2 facilitated the adaptation of breast epithelial cells to ER stress by supporting cell growth and protecting the cells from ER stress-induced cell death.

Conclusions

ERLIN2 may confer a selective growth advantage for breast cancer cells by facilitating a cytoprotective response to various cellular stresses associated with oncogenesis. The information provided here sheds new light on the mechanism of breast cancer malignancy
Snake venom toxin from vipera lebetina turanicainduces apoptosis of colon cancer cells via upregulation of ROS- and JNK-mediated death receptor expression
Authors: Park Mi Hee , Jo MiRan , Won Dohee , Song Ho Sueb , Han Sang Bae , Song Min Jong , Hong Jin Tae
Published: June 2012

Background

Abundant research suggested that the cancer cells avoid destruction by the immune system through down-regulation or mutation of death receptors. Therefore, it is very important that finding the agents that increase the death receptors of cancer cells. In this study, we demonstrated that the snake venom toxin fromVipera lebetina turanicainduce the apoptosis of colon cancer cells through reactive oxygen species (ROS) and c-Jun N-terminal kinases (JNK) dependent death receptor (DR4 and DR5) expression.

Methods

We used cell viability assays, DAPI/TUNEL assays, as well as western blot for detection of apoptosis related proteins and DRs to demonstrate that snake venom toxin-induced apoptosis is DR4 and DR5 dependent. We carried out transient siRNA knockdowns of DR4 and DR5 in colon cancer cells.

Results

We showed that snake venom toxin inhibited growth of colon cancer cells through induction of apoptosis. We also showed that the expression of DR4 and DR5 was increased by treatment of snake venom toxin. Moreover, knockdown of DR4 or DR5 reversed the effect of snake venom toxin. Snake venom toxin also induced JNK phosphorylation and ROS generation, however, pretreatment of JNK inhibitor and ROS scavenger reversed the inhibitory effect of snake venom toxin on cancer cell proliferation, and reduced the snake venom toxin-induced upregulation of DR4 and DR5 expression.

Conclusions

Our results indicated that snake venom toxin could inhibit human colon cancer cell growth, and these effects may be related to ROS and JNK mediated activation of death receptor (DR4 and DR5) signals.
The heat shock protein-90 co-chaperone, Cyclophilin 40, promotes ALK-positive, anaplastic large cell lymphoma viability and its expression is regulated by the NPM-ALK oncoprotein
Authors: Pearson Joel D , Mohammed Zubair , Bacani Julinor T C , Lai Raymond , Ingham Robert J
Published: June 2012

Background

Anaplastic lymphoma kinase-positive, anaplastic large cell lymphoma (ALK+ ALCL) is a T cell lymphoma defined by the presence of chromosomal translocations involving the ALK tyrosine kinase gene. These translocations generate fusion proteins (e.g. NPM-ALK) with constitutive tyrosine kinase activity, which activate numerous signalling pathways important for ALK+ ALCL pathogenesis. The molecular chaperone heat shock protein-90 (Hsp90) plays a critical role in allowing NPM-ALK and other signalling proteins to function in this lymphoma. Co-chaperone proteins are important for helping Hsp90 fold proteins and for directing Hsp90 to specific clients; however the importance of co-chaperone proteins in ALK+ ALCL has not been investigated. Our preliminary findings suggested that expression of the immunophilin co-chaperone, Cyclophilin 40 (Cyp40), is up-regulated in ALK+ ALCL by JunB, a transcription factor activated by NPM-ALK signalling. In this study we examined the regulation of the immunophilin family of co-chaperones by NPM-ALK and JunB, and investigated whether the immunophilin co-chaperones promote the viability of ALK+ ALCL cell lines.

Methods

NPM-ALK and JunB were knocked-down in ALK+ ALCL cell lines with siRNA, and the effect on the expression of the three immunophilin co-chaperones: Cyp40, FK506-binding protein (FKBP) 51, and FKBP52 examined. Furthermore, the effect of knock-down of the immunophilin co-chaperones, either individually or in combination, on the viability of ALK+ ALCL cell lines and NPM-ALK levels and activity was also examined.

Results

We found that NPM-ALK promoted the transcription of Cyp40 and FKBP52, but only Cyp40 transcription was promoted by JunB. We also observed reduced viability of ALK+ ALCL cell lines treated with Cyp40 siRNA, but not with siRNAs directed against FKBP52 or FKBP51. Finally, we demonstrate that the decrease in the viability of ALK+ ALCL cell lines treated with Cyp40 siRNA does not appear to be due to a decrease in NPM-ALK levels or the ability of this oncoprotein to signal.

Conclusions

This is the first study demonstrating that the expression of immunophilin family co-chaperones is promoted by an oncogenic tyrosine kinase. Moreover, this is the first report establishing an important role for Cyp40 in lymphoma.