bluuebunny/crossref_metadata_2025 huggingface dataset:
C1-inhibitor autoantibodies in SLE
Authors: Mészáros T. , Füst G. , Farkas H. , Jakab L. , Temesszentandrási G. , Nagy G. , Kiss E. , Gergely P. , Zeher M. , Griger Z. , Czirják L. , Hóbor R. , Haris A. , Polner K. , Varga L.
Published: January 2010

The presence of anti-C1-inhibitor (anti-C1-INH) autoantibodies is a hallmark of acquired C1-inhibitor deficiency. However, only scarce data are available on their prevalence, diagnostic value, and/or significance in systemic lupus erythematosus (SLE). In a multicentre study, we determined the levels of autoantibodies to C1-inhibitor in sera from 202 patients with SLE and 134 healthy controls. Additional clinical and laboratory parameters, such as organ involvement, as well as anti-C1q, anti-double-stranded DNA antibody, erythrocyte sedimentation rate, C-reactive protein, C3 and C4 serum complement levels have been studied in patients. The level of anti-C1-INH IgG was significantly higher (p = 0.034) in SLE patients, than in the controls. A high anti-C1-INH level of ≥0.4 U/ml (mean of controls + 2 SD) was found in 17% of the patients, but in only 4% of the controls (p = 0.0003). The SLEDAI score was significantly higher (p = 0.048) and the duration of SLE was significantly longer (p = 0.0004) among patients with elevated anti-C1-INH levels compared with patients without this autoantibody (median disease duration 8 vs. 17 years, respectively). Anti-C1-INH level was not correlated with any other laboratory parameter or organ manifestation of the disease. These findings indicate that the anti-C1-INH level is higher in SLE patients than in healthy controls and furthermore, the anti-C1-INH level correlates with the duration and activity of the disease. Lupus (2010) 19, 634—638.
What part of ‘No’ don’t you understand? —Talking the Tough Stuff of the Bible: A Creative Reading of the Rape of Tamar—2 Sam. 13:1-22
Authors: Casey Keree Louise
Published: January 2010

The Bible is full of stories. Many are read each week as part of the liturgy of the Service of the Lord’s Day. They are reflected on during personal and group Bible studies—even in Sunday school. They are stories that inspire, challenge, encourage and nurture our journey of Christian faith. However, there are also stories in the Bible we would prefer were not re-told. These particular stories confront, offend and profoundly challenge our understanding of God. We ask where God is in this story. Why is it in the canon of Holy Scripture? What can we learn from the re-telling of this story in our context? Where is the Good News? These are the‘tough stuff stories of the Bible —their subject matter embarrassing to our thinking, faith and theology in the 21st century. What part of ‘No’ don’t you understand? is one of those stories. It is a story that must always be re-told.
Criminology in and of China: Discipline and Power
Authors: Hebenton Bill , Jou Susyan
Published: January 2010

This sociohistorical study of the development of criminology in the People’s Republic of China not only considers available primary and secondary sources but also directly draws upon fieldwork interviews conducted with prominent scholars in China in 2007. Crime has been a silent partner in Chinese modernization, and law and order have been as central to the Chinese ruling elite’s priorities as the promise of prosperity and economic growth. Criminology as a field of study with recognized scholars and research publications has been established in China, and our article critically examines the development, focus and scope, direction and trends, and underpinning theories.
Chinese Policing in a Time of Transition, 1978-2008
Authors: Sun Ivan Y. , Yuning Wu
Published: January 2010

This article examines the development of policing in China over several historical periods. It consists of three major parts. The first section provides a brief historical review of Chinese policing before 1949 and between 1949 and 1977 with the emphasis on mass-line policing. The second section, which is the core of the study, discusses several broad dimensions associated with the so-called strike-hard policing and community policing adopted by the Chinese police since 1978. These pivotal areas include policies and laws, organizational structure and development, field practices and effectiveness, and police accountability and reform. The last section discusses critical issues for the future development of Chinese policing and specifies directions for future research on Chinese policing.
The Resurgence of Prostitution in China: Explanations and Implications
Authors: Liu Min , Finckenauer James O.
Published: January 2010

Prostitution reemerged in China in the 1980s and has become rampant ever since then—attracting enormous attention and academic interest. This article examines the history of prostitution in China, from its roots to the causes of its resurgence. It also examines China’s legal responses and policies and their limited effectiveness in containing the growth of the sex industry. In considering the possible relationship between prostitution and human trafficking, this article intends to improve our understanding of the link between the sex industry and sex trafficking, and to push for empirical studies on Chinese women working as prostitutes.
Official Corruption During China’s Economic Transition: Historical Patterns, Characteristics, and Government Reactions
Authors: Deng Xiaogang , Zhang Lening , Leverentz Andrea
Published: January 2010

Using available information and data, this study examines the historical patterns and characteristics of official corruption in contemporary China. The study identifies four waves of official corruption associated with different stages of the nation’s economic reform. Each wave of corruption has different forms and targets. In our analysis, the general trend is that as the nation’s economic reforms move forward, official corruption in China is becoming more serious and pervasive with more money and higher ranked officials involved in corruption cases. This is raising a serious challenge to Chinese authorities who have shown a willingness and effort to control official corruption.We conclude that without fundamental political reform, official corruption is not likely to be controlled in China.
Internet Development, Censorship, and Cyber Crimes in China
Authors: Liang Bin , Lu Hong
Published: January 2010

Since its first Internet connection with the global computer network in 1994, China has witnessed explosive Internet development. By the end of 2008, China replaced the United States as the largest Internet user of the world. Although China enjoyed tremendous economic benefits from Internet development, the Chinese government has tried to maintain tight control over the telecommunications industry and the public Internet use, and fight increasing cyber crimes. In this article, we first review historical development of Internet use in China and then focus on China’s Internet censorship and its regulatory control. Next, we explore how the Internet is actively utilized by both the government and the public to serve political and civic functions. Finally, we discuss cyber crimes as an emergent form of crime in China and examine how the Chinese government reacts to these offenses. Lessons from Internet use and regulation in China are also discussed within the context of China’s economic, political, and legal conditions.
Gregory Research Beliefs Scale: Factor Structure and Internal Consistency
Authors: Gregory Virgil L.
Published: January 2010

Objective: This study evaluates the factor structure and internal consistency of the Gregory Research Beliefs Scale (GRBS). Method: Data were collected from subject matter experts, a pilot study, an online sample, and a classroom sample. Psychometric analyses were conducted after combining the online and classroom samples. Results: An a priori four-factor model was not supported via confirmatory factor analysis. Principal component analyses were used to reduce the items to a one-factor model with salient structure coefficients, face validity, and a Cronbach’s alpha of 0.93. Discussion and Applications: Future research should evaluate factor invariance and the construct and criterion validity of the GRBS. However, given the limitations of scales that measure similar constructs, the GRBSs brings the social work profession closer to effectively quantifying an internally consistent and homogenous latent variable that may be related to evidence-based practice.
A Couples Advance Directives Interview Using the Five Wishes Questionnaire
Authors: Eckstein Daniel , Mullener Bill
Published: January 2010

This article provides couples an opportunity to consider personal wishes for end-of-life decision making. There is brief overview of some of the issues and organizations addressing advanced directives. A portion of the Five Wishes1 questionnaire, presented with permission of the Aging with Dignity organization, will be presented as a resource for the interviewing process. A sample case study is presented.
A One Year Trial of Methylphenidate in the Treatment of ADHD
Authors: Wender Paul H. , Reimherr Frederick W. , Marchant Barrie K. , Sanford Mary Eve , Czajkowski Laura A. , Tomb David A.
Published: January 2010

Objective: To determine the effects of long-term methylphenidate treatment on symptom severity and social adjustment in adult ADHD. Method: Adults ( n = 116) meeting operational diagnostic criteria for ADHD (the “Utah Criteria”) entered a randomized double-blind crossover trial of methylphenidate and placebo. Participants who improved on immediate-release methylphenidate entered a 12-month, open-label trial. Outcomes were assessed using the Wender-Reimherr Adult Attention Deficit Disorder Scale (WRAADDS), Clinical Global Impression—Improvement (CGI-I), global assessment of functioning (GAF), and the Weissman Social Adjustment Scale (WSAS). Results: In the double-blind trial more patients improved (50% reduction of symptoms) receiving methylphenidate (74%) than placebo (21%, p = .001). During the open-label trial, symptom severity decreased 80% from baseline, and the WSAS decreased >50% in all subscales. The average GAF improved significantly ( p < .0001). Conclusion: ADHD adults, who responded to methylphenidate in a short-tem, placebo-controlled trial, responded to long-term treatment with marked improvements in ADHD symptoms and psychosocial functioning.
Is Behavioral Regulation in Children With ADHD Aggravated by Comorbid Anxiety Disorder?
Authors: Sørensen Lin , Plessen Kerstin J. , Nicholas Jude , Lundervold Astri J.
Published: January 2010

Background: The present study investigated the impact of coexisting anxiety disorder in children with ADHD on their ability to regulate behavior. Method: Parent reports on the Behavior Rating Inventory of Executive Function (BRIEF) in a comorbid group of children with ADHD and anxiety ( n = 11) were compared to BRIEF reports in a group of children with a “pure” ADHD ( n = 23), a “pure” anxiety ( n = 24) and a group without any diagnosis ( n = 104) in a 2 (ADHD vs. no ADHD) × 2 (anxiety vs. no anxiety) design. Results: The children with ADHD and anxiety disorder scored significantly higher on the Inhibit scale than children within the other three groups. Main effects of diagnosis appeared in ADHD children on the Inhibit, Emotional Control, and Working Memory scales, and on the Shift and Emotional Control scales in anxious children. Conclusion: The results indicate that a behavioral dysregulation in ADHD children is aggravated by comorbid anxiety.
A Comprehensive Review and Meta-Analysis of the Social Stories Literature
Authors: Test David W. , Richter Sharon , Knight Victoria , Spooner Fred
Published: January 2010

This comprehensive review of Social Story™ literature included (a) a descriptive review, (b) an analysis of research quality, and (c) a meta-analysis using percentage of nonoverlapping data. In the review, 28 studies were included; 18 were included in the meta-analysis. Descriptive results highlighted information on participants, dependent variables, independent variables, and alignment with Social Stories standards. Analysis of research quality yielded strengths in participant description and selection of socially important dependent variables, whereas weaknesses were identified in data collection related to procedural reliability and social validity of procedures. Finally, percentage of nonoverlapping data ranged from 0 to 97.7%, with a median of 50%. Suggestions for future research, implications for practitioners, and limitations are provided.
Effect of Bee Venom on Transforming Growth Factor–β1-Treated Hepatocytes
Authors: Park Jung-Hyun , Kim Kyung-Hyun , Kim Soo-Jung , Lee Woo-Ram , Lee Kwang-Gill , Park Ji-Hyun , Park Kwan-Kyu
Published: January 2010

Bee venom (BV) has been used as treatment against a wide variety of ailments, including inflammatory diseases. Various studies have demonstrated anti-inflammatory and anticancer effects of BV. Transforming growth factor (TGF)–β1 induces hepatocyte apoptosis via the mitochondrial permeability transition. However, there is no evidence or information regarding the antiapoptotic effect of BV on hepatocytes. The authors investigated the antiapoptotic effect of BV on TGF-β1-treated hepatocytes. The results showed significant protection from DNA damage by BV treatment compared to corresponding TGF-β1-treated hepatocytes without BV. BV suppressed TGF-β1-induced activation of the bcl-2 family and caspase family of proteins, which resulted in inhibition of poly ADP-ribose polymerase (PARP) cleavage. Furthermore, BV is not cytotoxic in the low concentrations used in this study. Low concentrations of BV potently suppress the apoptotic response in TGF-β1-treated hepatocytes; therefore, BV may have therapeutic potential for the treatment of liver diseases.
Bibliometrics as a Performance Measurement Tool for Research Evaluation: The Case of Research Funded by the National Cancer Institute of Canada
Authors: Campbell David , Picard-Aitken Michelle , Côté Grégoire , Caruso Julie , Valentim Rodolfo , Edmonds Stuart , Williams Gregory Thomas , Macaluso Benoît , Robitaille Jean-Pierre , Bastien Nicolas , Laframboise Marie-Claude , Lebeau Louis-Michel , Mirabel Philippe , Larivière Vincent , Archambault Éric
Published: January 2010

As bibliometric indicators are objective, reliable, and cost-effective measures of peer-reviewed research outputs, they are expected to play an increasingly important role in research assessment/management. Recently, a bibliometric approach was developed and integrated within the evaluation framework of research funded by the National Cancer Institute of Canada (NCIC). This approach helped address the following questions that were difficult to answer objectively using alternative methods such as program documentation review and key informant interviews: (a) Has the NCIC peer-review process selected outstanding Canadian scientists in cancer research? (b) Have the NCIC grants contributed to increasing the scientific performance of supported researchers? (c) How do the NCIC-supported researchers compare to their neighbors supported by the U.S. National Cancer Institute? Using the NCIC evaluation as a case study, this article demonstrates the usefulness of bibliometrics to address key evaluation questions and discusses its integration, along complementary indicators (e.g., peer ratings), in a practice-driven research evaluation continuum.
Becoming a leader: A co-produced autoethnographic exploration of situated learning of leadership practice
Authors: Kempster Steve , Stewart James
Published: January 2010

The article examines the development of situated leadership practice through an autoethnographic study of the first three months of being in the role of a chief operating officer. The argument for using an autoethnographic approach is in response to the dearth of in-depth research on the development of leadership practice from a relational, social and situated perspective. The article makes a contribution to management learning by exploring aspects of situated curriculum within a manager’s legitimate participation influencing the development of situated leadership practice.
Evaluating the Matrix Language Frame model on the basis of a Russian—Estonian codeswitching corpus
Authors: Zabrodskaja Anastassia
Published: January 2010

This article focuses on the question to what degree typological characteristics of the languages involved interact with the Matrix Language vs. Embedded Language and Content Morpheme vs. System Morpheme distinctions. In addition, the integration of Estonian items in Russian—Estonian codeswitched sentences is described, because the extent of integration of Estonian items into the Russian matrix is closely related to matrix language determination. Both Estonian and Russian have a complex inflectional morphology. Full integration of an Estonian item into Russian means gender and case assignment, but in fact this does not occur in all codeswitched instances. Russian—Estonian data demonstrate a wider range of possibilities than just fully integrated and completely unintegrated items. Estonian items may be integrated phonologically into Russian (e.g. regarding vowel length or stress), but morphological and phonological integration do not depend on each other: Estonian items may show extensive phonological but no morphological integration into Russian and vice versa. Bilingual data show that the matrix language cannot be determined by analyzing the morphosyntactic level only; the degree of phonological integration of codeswitched words should also be taken into account. Thus, the morphosyntactic bias in the Matrix Language Frame model, meaning that phonological adaptation has no influence at all on matrix language assignment, is criticized.
Russian influence on the Ižma Komi dialect
Authors: Leinonen Marja
Published: January 2010

The article deals with the results of the language contacts between Russian and Komi (Komi-Zyrian), especially one of its dialects, that of Ižma, in the north-eastern corner of European Russia. The long-term contacts are discussed in a socio-historical context, which explains how the present minority status of Komi has occurred. The structural, lexical, and pragmatic unilateral convergence of Komi with Russian is explored. A case study with material from a TV interview — a semi-official speech of an Ižma speaker — illustrates the introduction of Russian lexemes and constructions into Komi via codeswitching and borrowing.
The use of Russian conjunctions in the speech of bilingual Kazakhs
Authors: Muhamedowa Raihan
Published: January 2010

The article analyzes the insertion of the Russian causal clause conjunction поTому чTо (‘because’) and the complementizer чTо (‘that’) in Kazakh clauses. The study is based on taped interviews made in Almaty, Kazakhstan. The analysis is based on the main concepts of the Matrix Language Frame (MLF) model. Kazakh, a Turkic language, is claimed to have non-finite and finite subordination patterns but the common way of modelling causal clauses is the left-branching non-finite structure. The study shows that this type of genuine Kazakh causal clause is totally absent in the speech of bilinguals. Because of the strong Russian influence, the right-branching structure with a finite verb becomes common. The study records a syntactic change in spoken Kazakh. Kazakh causal clauses become more similar to the Russian pattern. The complement clauses are not under the same strong Russian influence as causal clauses. Russian complementizer чTо occurs mostly as a part of a preceding Russian main clause. The data also offer examples of composite matrix language, a concept of the MFL model where two languages provide the syntax of a bilingual clause.
The Taimyr Pidgin Russian morphology enigma
Authors: Stern Dieter
Published: January 2010

Unlike prototypical pidgins, Taimyr Pidgin Russian (TPR) has adopted almost the complete set of verbal inflexions from its lexifier. This might be indicative of a social setting differing in a significant way from the usual pidginization scenario. Taking into account the ecolinguistic setting under which TPR evolved, a general picture of how TPR may have acquired its unique morphological peculiarities will be drawn. This article will try to piece the relevant sociohistorical evidence together and argue for TPR representing a pidgin of a different type, as it reflects in its morphological frame a less segregated contact history between the indigenous population of northern Siberia and the Russian newcomers. In the end TPR may have more in common with L2-varieties of old-settlers’ Russian, like Kamchadal Russian used by Itelmens, than with prototypical pidgins, thus constituting a Russian equivalent in type to pidgins in the colonial sphere of western nations.
Trasjanka: A code of rural migrants in Minsk
Authors: Liskovets Irina
Published: January 2010

The article deals with an oral speech phenomenon widespread in the Republic of Belarus, where it is known as trasjanka. This code originated through constant contact between Russian and Belarusian, two closely related East Slavonic languages. Discussed are the main features of this code (as used in the city of Minsk), the sources of its origin, different linguistic definitions and the attitude towards this code from those who dwell in the city of Minsk. Special attention is paid to the problem of distinction between trasjanka and different forms of codeswitching, also widely used in the Minsk language community.
A Systematic Review of Narrative-Based Language Intervention With Children Who Have Language Impairment
Authors: Petersen Douglas B.
Published: January 2010

This systematic review focuses on research articles published since 1980 that assess outcomes of narrative-based language intervention for preschool and school-age children with language impairment. The author conducted a comprehensive search of electronic databases and hand searches of other sources for studies using all research designs except nonexperimental case studies. The results of the studies were converted to a common metric using effect sizes. The review yielded nine studies that met inclusion criteria. The majority of studies reported moderate to large effect sizes for narrative macrostructure and microstructure. Although the results of the studies were generally positive, each of the studies had a limited number of participants, limited experimental control, and considerable variation in the procedures and materials used. Clinicians should be cautious when interpreting the results of these studies. Narrative intervention is at an emerging stage of evidence and needs further investigation.
Decision Making of Parents of Children With Autism Spectrum Disorder Concerning Augmentative and Alternative Communication in Hungary
Authors: Serpentine Elizabeth C. , Tarnai Balazs , Drager Kathryn D. R. , Finke Erinn H.
Published: January 2010

A qualitative interview methodology was used to investigate the perspectives of 10 Hungarian parents of children with autism spectrum disorder (ASD) concerning their decision-making processes undertaken to make communication intervention decisions for their children. Six themes were identified from the data: (a) sources of information, (b) interventions to support communication, (c) intervention outcomes, (d) reasons for adding or discontinuing interventions, (e) desired interventions, and (f) decision-making processes. Parents in Hungary used a variety of sources to find information about communication interventions and had differing expectations of these interventions. They expressed a variety of reasons for adding or discontinuing communication interventions. Additional results are discussed as they relate to the themes and with reference to published literature. Limitations to this research are presented, and several priorities for further research directions are offered.
Reflections on Salary Shares and Salary Caps
Authors: Zimbalist Andrew
Published: January 2010

This article takes a closer look at salary and revenue figures for the four major professional sports in the United States. It shows that the reporting typically offered in the popular media and often picked up in academic work can be rather misleading. The article first considers the conundrums in defining player compensation and then those connected to revenue. On the basis of adjusted data, the article proceeds to look at salary shares in revenue across the four leagues and considers the irony that the salary share in Major League Baseball (MLB) appears to be lower than the three leagues with a salary cap, the National Football League (NFL), National Basketball Association (NBA), and National Hockey League (NHL). It concludes with some analysis of the impact of salary caps and other mechanisms on controlling player costs.
Working in the Land of the Metricians
Authors: Berri David J. , Bradbury John Charles
Published: January 2010

The research of sports economists often addresses issues of interest to nonacademics. The shared interests often lead to interactions that have benefits and costs. The benefits center on nonacademic research—found in the ‘‘sabermetric’’ and ‘‘APBRmetric’’ communities—that can inform the work of academic economists studying sports. However, nonacademic research should be interpreted with caution because it is not subject to an academic peer review. This essay discusses how economists can benefit from sabermetric advances while avoiding its pitfalls.
Successful Viral Suppression With Subsequent Efavirenz-Based Regimen in HIV-1-Infected Patients Who Stop Nevirapine Prior to Discontinuation of the NRTI Backbone
Authors: Chimsuntorn Sukanya , Sungkanuparph Somnuek , Manosuthi Weerawat
Published: January 2010

Objective: To study antiviral response of efavirenz (EFV)-based antiretroviral therapy (ART) in HIV-1-infected patients who had previously discontinued nevirapine (NVP) and continued the nucleoside reverse transcriptase inhibitor (NRTI) backbone for 7 to 14 days after stopping NVP. Methods: A retrospective cohort study was conducted in patients who discontinued NVP. CD4 count and plasma HIV-1 RNA levels were monitored through 48 weeks of EFV-based regimen. Results: Forty-five patients were eligible with a mean ± SD age of 37 ± 11 years; 60% were males. Median (interquartile range [IQR]) baseline CD4 count was 43 (19-150) cells/mm3 and median (IQR) plasma HIV-1 RNA was 5.7 (5.3-5.9) log copies/mL. Median (IQR) duration from stopping NVP to initiating EFV was 13 (7-18) days. At 48 week, 33 (73.3%) of 45 patients achieved plasma HIV-1 RNA <50 copies/mL. At week 12, 24, and 48, median CD4 counts were 193, 238, and 268 cells/mm3, respectively (P < .05). No studied risk factor was associated with achieving HIV-1 RNA <50 copies/mL at 48 weeks (P > .05). Conclusion: The strategy of extended short half-life NRTIs in the regimen after discontinuation of NVP is justified.
Stroke Affects Locomotor Steering Responses to Changing Optic Flow Directions
Authors: Lamontagne Anouk , Fung Joyce , McFadyen Bradford , Faubert Jocelyn , Paquette Caroline
Published: January 2010

Background. Stroke patients manifest steering difficulties during walking, which may arise from an altered perception of visual motion. Objective. To examine the ability of stroke patients to control their heading direction while walking in a virtual environment (VE) describing translational optic flows (OFs) expanding from different directions. Methods. The authors evaluated 10 stroke patients and 11 healthy people while they were walking overground and visualizing a VE in a helmet-mounted display. Participants were instructed to walk straight in the VE and were randomly exposed to an OF having a focus of expansion (FOE) located in 5 possible locations (0°, ±20°, and ±40° to the right or left). The body’s center of mass (CoM) trajectory, heading direction, and horizontal body reorientation were recorded with a Vicon-512 system. Results. Healthy participants veered opposite to the FOE location in the physical world, with larger deviations occurring at the most eccentric FOE locations. Stroke patients displayed altered steering behaviors characterized either by an absence of CoM trajectory corrections, multiple errors in the heading direction, or systematic veering to the nonparetic side. Both groups displayed relatively small CoM trajectory corrections that led to large virtual heading errors. Conclusions. The control of heading of locomotion in response to different OF directions is affected by stroke. An altered perception of heading direction and/or a poor integration of sensory and motor information are likely causes. This altered response to OF direction while walking may contribute to steering difficulties after stroke.
Before the Law: Animals in a Biopolitical Context
Authors: Wolfe Cary
Published: January 2010

Using examples such as factory farming and the recent decision by the Spanish Parliament to grant fundamental rights to great apes, this commentary explores the extent to which our current legal frameworks (including the legal discourse of “rights”) provide satisfactory responses to the question of justice for non-human animals. After briefly sketching appeals to the rights model (both pro and con) for non-human animals in legal pragmatism and in animal rights philosophy, I turn to recent work in biopolitical theory to rearticulate not just the ethical but also the political status of our treatment of non-human animals.
Anti-TNF therapy in ankylosing spondylitis: insights for the clinician
Authors: Coates Laura C. , Marzo-Ortega Helena , Bennett Alexander N. , Emery Paul
Published: January 2010

The introduction of tumour necrosis factor (TNF)-blocking therapy has revolutionized the management of ankylosing spondylitis (AS) over the last decade. This review highlights the current evidence relating to the use of TNF-blocking therapy in AS. International guidelines for the use of TNF blockers in AS are summarized. An outline of the evidence for efficacy and safety of these drugs is included, highlighting recent data from registries and real-life observational studies. Such cohort data is also reviewed highlighting the evidence for ‘switching’ TNF blockers in AS in the case of non-response or adverse events. The potential new application of TNF blockers in preradiographic axial spondyloarthropathy (SpA) or ‘early AS’ is discussed with reviews of two recent studies in this area. Finally research into the possible additional impacts of TNF therapies is reviewed. The question of whether TNF blockers are truly disease modifying in AS remains unanswered with conflicting reports. The additional burden of AS in terms of cardiovascular disease is now becoming understood. Recent data from basic science studies highlights the potential impact of TNF blockers on this excess cardiovascular morbidity and mortality. Future studies and registry data will be able to assess whether TNF blockers have an additional role in controlling systemic inflammation and its associated cardiovascular risk.
Irradiation and IL-15 promote loss of CD8 T-cell tolerance in response to lymphopenia
Authors: Oelert Thilo , Papatriantafyllou Maria , Pougialis Georg , Hämmerling Günter J. , Arnold Bernd , Schüler Thomas
Published: January 2010

Functional inactivation of self-reactive T lymphocytes contributes to the maintenance of immunologic self-tolerance. At the same time, tolerance induction limits immune responses against tumors expressing tolerizing self-antigens. Some cancer therapies include the adoptive transfer of tumor-reactive T lymphocytes into lymphopenic patients. Lymphopenia provides an activation signal to T lymphocytes, which undergo lymphopenia-induced proliferation (LIP), acquire effector functions, and reject tumors. However, it is so far unknown to which extent LIP may result in reversal of established antigen-specific CD8 T-cell tolerance. Here, we report that neonatally induced dominant CD8 T-cell tolerance remained stable under lymphopenic conditions also in the presence of systemic inflammation induced by Toll-like receptor ligands. However, when lymphopenic recipients were irradiated, the tolerant status was lost, because CD8 T cells acquired effector functions in an interleukin-15–dependent fashion and efficiently rejected tumors. In conclusion, we show that lymphopenia is not sufficient to break CD8 T-cell tolerance. Furthermore, we demonstrate that pretreatment regimens are crucial to circumvent this problem and to optimize adoptive T-cell therapy.
The ubiquitin-activating enzyme E1 as a therapeutic target for the treatment of leukemia and multiple myeloma
Authors: Xu G. Wei , Ali Mohsin , Wood Tabitha E. , Wong Derek , Maclean Neil , Wang Xiaoming , Gronda Marcela , Skrtic Marko , Li Xiaoming , Hurren Rose , Mao Xinliang , Venkatesan Meenakshi , Zavareh Reza Beheshti , Ketela Troy , Reed John C. , Rose David , Moffat Jason , Batey Robert A. , Dhe-Paganon Sirano , Schimmer Aaron D.
Published: January 2010

The proteasomal pathway of protein degradation involves 2 discrete steps: ubiquitination and degradation. Here, we evaluated the effects of inhibiting the ubiquitination pathway at the level of the ubiquitin-activating enzyme UBA1 (E1). By immunoblotting, leukemia cell lines and primary patient samples had increased protein ubiquitination. Therefore, we examined the effects of genetic and chemical inhibition of the E1 enzyme. Knockdown of E1 decreased the abundance of ubiquitinated proteins in leukemia and myeloma cells and induced cell death. To further investigate effects of E1 inhibition in malignancy, we discovered a novel small molecule inhibitor, 3,5-dioxopyrazolidine compound, 1-(3-chloro-4-fluorophenyl)-4-[(5-nitro-2-furyl)methylene]-3,5-pyrazolidinedione (PYZD-4409). PYZD-4409 induced cell death in malignant cells and preferentially inhibited the clonogenic growth of primary acute myeloid leukemia cells compared with normal hematopoietic cells. Mechanistically, genetic or chemical inhibition of E1 increased expression of E1 stress markers. Moreover, BI-1 overexpression blocked cell death after E1 inhibition, suggesting ER stress is functionally important for cell death after E1 inhibition. Finally, in a mouse model of leukemia, intraperitoneal administration of PYZD-4409 decreased tumor weight and volume compared with control without untoward toxicity. Thus, our work highlights the E1 enzyme as a novel target for the treatment of hematologic malignancies.
A variant allele of Growth Factor Independence 1 (GFI1) is associated with acute myeloid leukemia
Authors: Khandanpour Cyrus , Thiede Christian , Valk Peter J. M. , Sharif-Askari Ehssan , Nückel Holger , Lohmann Dietmar , Horsthemke Bernhard , Siffert Winfried , Neubauer Andreas , Grzeschik Karl-Heinz , Bloomfield Clara D. , Marcucci Guido , Maharry Kati , Slovak Marilyn L. , van der Reijden Bert A. , Jansen Joop H. , Schackert Hans K. , Afshar Khashayar , Schnittger Susanne , Peeters Justine K. , Kroschinsky Frank , Ehninger Gerhard , Lowenberg Bob , Dührsen Ulrich , Möröy Tarik
Published: January 2010

The GFI1 gene encodes a transcriptional repressor, which regulates myeloid differentiation. In the mouse, Gfi1 deficiency causes neutropenia and an accumulation of granulomonocytic precursor cells that is reminiscent of a myelodysplastic syndrome. We report here that a variant allele of GFI1 (GFI136N) is associated with acute myeloid leukemia (AML) in white subjects with an odds ratio of 1.6 (P < 8 × 10−5). The GFI136N variant occurred in 1806 AML patients with an allele frequency of 0.055 compared with 0.035 in 1691 healthy control patients in 2 independent cohorts. We observed that both GFI1 variants maintain the same activity as transcriptional repressors but differ in their regulation by the AML1/ETO (RUNX1/RUNX1T1) fusion protein produced in AML patients with a t(8;21) translocation. AML1/ETO interacts and colocalizes with the more common GFI136S form in the nucleus and inhibits its repressor activity. However, the variant GFI136N protein has a different subnuclear localization than GFI136S. As a consequence, AML1/ETO does not colocalize with GFI136N and is unable to inhibit its repressor activity. We conclude that both variants of GFI1 differ in their ability to be regulated by interacting proteins and that the GFI136N variant form exhibits distinct biochemical features that may confer a predisposition to AML.
A novel approach to preventing the hemolysis of paroxysmal nocturnal hemoglobinuria: both complement-mediated cytolysis and C3 deposition are blocked by a monoclonal antibody specific for the alternative pathway of complement
Authors: Lindorfer Margaret A. , Pawluczkowycz Andrew W. , Peek Elizabeth M. , Hickman Kimberly , Taylor Ronald P. , Parker Charles J.
Published: January 2010

The clinical hallmark of paroxysmal nocturnal hemoglobinuria (PNH) is chronic intravascular hemolysis that is a consequence of unregulated activation of the alternative pathway of complement (APC). Intravascular hemolysis can be inhibited in patients by treatment with eculizumab, a monoclonal antibody that binds complement C5 thereby preventing formation of the cytolytic membrane attack complex of complement. However, in essentially all patients treated with eculizumab, persistent anemia, reticulocytosis, and biochemical evidence of hemolysis are observed; and in a significant proportion, their PNH erythrocytes become opsonized with complement C3. These observations suggest that PNH patients treated with eculizumab are left with clinically significant immune-mediated hemolytic anemia because the antibody does not block APC activation. With a goal of improving PNH therapy, we characterized the activity of anti-C3b/iC3b monoclonal antibody 3E7 in an in vitro model of APC-mediated hemolysis. We show that 3E7 and its chimeric-deimmunized derivative H17 block both hemolysis and C3 deposition on PNH erythrocytes. The antibody is specific for the APC C3/C5 convertase because classical pathway–mediated hemolysis is unaffected by 3E7/H17. These findings suggest an approach to PNH treatment in which both intravascular and extravascular hemolysis can be inhibited while preserving important immune functions of the classical pathway of complement.
Thioredoxins function as deglutathionylase enzymes in the yeast Saccharomyces cerevisiae
Authors: Greetham Darren , Vickerstaff Jill , Shenton Daniel , Perrone Gabriel G , Dawes Ian W , Grant Chris M
Published: January 2010

Background

Protein-SH groups are amongst the most easily oxidized residues in proteins, but irreversible oxidation can be prevented by protein glutathionylation, in which protein-SH groups form mixed disulphides with glutathione. Glutaredoxins and thioredoxins are key oxidoreductases which have been implicated in regulating glutathionylation/deglutathionylation in diverse organisms. Glutaredoxins have been proposed to be the predominant deglutathionylase enzymes in many plant and mammalian species, whereas, thioredoxins have generally been thought to be relatively inefficient in deglutathionylation.

Results

We show here that the levels of glutathionylated proteins in yeast are regulated in parallel with the growth cycle, and are maximal during stationary phase growth. This increase in glutathionylation is not a response to increased reactive oxygen species generated from the shift to respiratory metabolism, but appears to be a general response to starvation conditions. Our data indicate that glutathionylation levels are constitutively high in all growth phases in thioredoxin mutants and are unaffected in glutaredoxin mutants. We have confirmed that thioredoxins, but not glutaredoxins, catalyse deglutathionylation of model glutathionylated substrates using purified thioredoxin and glutaredoxin proteins. Furthermore, we show that the deglutathionylase activity of thioredoxins is required to reduce the high levels of glutathionylation in stationary phase cells, which occurs as cells exit stationary phase and resume vegetative growth.

Conclusions

There is increasing evidence that the thioredoxin and glutathione redox systems have overlapping functions and these present data indicate that the thioredoxin system plays a key role in regulating the modification of proteins by the glutathione system.
The role of vasculature and blood circulation in zebrafish swimbladder development
Authors: Winata Cecilia Lanny , Korzh Svetlana , Kondrychyn Igor , Korzh Vladimir , Gong Zhiyuan
Published: January 2010

Background

Recently we have performed a detailed analysis of early development of zebrafish swimbladder, a homologous organ of tetrapod lung; however, the events of swimbladder development are still poorly characterized. Many studies have implicated the role of vascular system in development of many organs in vertebrates. As the swimbladder is lined with an intricate network of blood capillaries, it is of interest to investigate the role of the vascular system during early development of swimbladder.

Results

To investigate the role of endothelial cells (ECs) and blood circulation during development of the swimbladder, phenotypes of swimbladder were analysed at three different stages (~2, 3 and 5 dpf [day postfertilization]) in cloche (clo) mutant and Tnnt2 morphants, in the background of transgenic lines Et(krt4:EGFP)

sq33-2
and Et(krt4:EGFP)

sqet3
which express EGFP in the swimbladder epithelium and outer mesothelium respectively. Analyses of the three tissue layers of the swimbladder were performed using molecular markers hb9, fgf10a, acta2, and anxa5 to distinguish epithelium, mesenchyme, and outer mesothelium. We showed that the budding stage was independent of ECs and blood flow, while early epithelial growth, mesenchymal organization and its differentiation into smooth muscle, as well as outer mesothelial organization, were dependent on ECs. Blood circulation contributed to later stage of epithelial growth, smooth muscle differentiation, and organization of the outer mesothelium. Inflation of the swimbladder was also affected as a result of absence of ECs and blood flow.

Conclusion

Our data demonstrated that the vascular system, though not essential in swimbladder budding, plays an important role in the development of the swimbladder starting from the early growth stage, including mesenchyme organization and smooth muscle differentiation, and outer mesothelial organization, which in turn may be essential for the function of the swimbladder as reflected in its eventual inflation.
Genomics Portals: integrative web-platform for mining genomics data
Authors: Shinde Kaustubh , Phatak Mukta , Johannes Freudenberg M , Chen Jing , Li Qian , Vineet Joshi K , Hu Zhen , Ghosh Krishnendu , Meller Jaroslaw , Medvedovic Mario
Published: January 2010

Background

A large amount of experimental data generated by modern high-throughput technologies is available through various public repositories. Our knowledge about molecular interaction networks, functional biological pathways and transcriptional regulatory modules is rapidly expanding, and is being organized in lists of functionally related genes. Jointly, these two sources of information hold a tremendous potential for gaining new insights into functioning of living systems.

Results

Genomics Portals platform integrates access to an extensive knowledge base and a large database of human, mouse, and rat genomics data with basic analytical visualization tools. It provides the context for analyzing and interpreting new experimental data and the tool for effective mining of a large number of publicly available genomics datasets stored in the back-end databases. The uniqueness of this platform lies in the volume and the diversity of genomics data that can be accessed and analyzed (gene expression, ChIP-chip, ChIP-seq, epigenomics, computationally predicted binding sites, etc), and the integration with an extensive knowledge base that can be used in such analysis.

Conclusion

The integrated access to primary genomics data, functional knowledge and analytical tools makes Genomics Portals platform a unique tool for interpreting results of new genomics experiments and for mining the vast amount of data stored in the Genomics Portals backend databases. Genomics Portals can be accessed and used freely at http://GenomicsPortals.org.
Regional regulation of transcription in the chicken genome
Authors: Nie Haisheng , Crooijmans Richard PMA , Bastiaansen John WM , Megens Hendrik-Jan , Groenen Martien AM
Published: January 2010

Background

Over the past years, the relationship between gene transcription and chromosomal location has been studied in a number of different vertebrate genomes. Regional differences in gene expression have been found in several different species. The chicken genome, as the closest sequenced genome relative to mammals, is an important resource for investigating regional effects on transcription in birds and studying the regional dynamics of chromosome evolution by comparative analysis.

Results

We used gene expression data to survey eight chicken tissues and create transcriptome maps for all chicken chromosomes. The results reveal the presence of two distinct types of chromosomal regions characterized by clusters of highly or lowly expressed genes. Furthermore, these regions correlate highly with a number of genome characteristics. Regions with clusters of highly expressed genes have higher gene densities, shorter genes, shorter average intron and higher GC content compared to regions with clusters of lowly expressed genes. A comparative analysis between the chicken and human transcriptome maps constructed using similar panels of tissues suggests that the regions with clusters of highly expressed genes are relatively conserved between the two genomes.

Conclusions

Our results revealed the presence of a higher order organization of the chicken genome that affects gene expression, confirming similar observations in other species. These results will aid in the further understanding of the regional dynamics of chromosome evolution.

The microarray data used in this analysis have been submitted to NCBI GEO database under accession number GSE17108. The reviewer access link is: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?token=tjwjpscyceqawjk&acc=GSE17108
Transcriptome analysis of the sex pheromone gland of the noctuid moth Heliothis virescens
Authors: Vogel Heiko , Heidel Andrew J , Heckel David G , Groot Astrid T
Published: January 2010

Background

The chemical components of sex pheromones have been determined for more than a thousand moth species, but so far only a handful of genes encoding enzymes responsible for the biosynthesis of these compounds have been identified. For understanding the evolution of moth sexual communication, it is essential to know which genes are involved in the production of specific pheromone components and what controls the variation in their relative frequencies in the pheromone blend. We used a transcriptomic approach to characterize the pheromone gland of the Noctuid moth Heliothis virescens, an important agricultural pest, in order to obtain substantial general sequence information and to identify a range of candidate genes involved in the pheromone biosynthetic pathway.

Results

To facilitate identifying sets of genes involved in a broad range of processes and to capture rare transcripts, we developed our majority of ESTs from a normalized cDNA library of Heliothis virescens pheromone glands (PG). Combining these with a non-normalized library yielded a total of 17,233 ESTs, which assembled into 2,082 contigs and 6,228 singletons. Using BLAST searches of the NR and Swissprot databases we were able to identify a large number of putative unique gene elements (unigenes), which we compared to those derived from previous transcriptomic surveys of the larval stage of Heliothis virescens. The distribution of unigenes among GO Biological Process functional groups shows an overall similarity between PG and larval transcriptomes, but with distinct enrichment of specific pathways in the PG. In addition, we identified a large number of candidate genes in the pheromone biosynthetic pathways.

Conclusion

These data constitute one of the first large-scale EST-projects for Noctuidae, a much-needed resource for exploring these pest species. Our analysis shows a surprisingly complex transcriptome and we identified a large number of potential pheromone biosynthetic pathway and immune-related genes that can be applied to population and systematic studies of Heliothis virescens and other Noctuidae.