bluuebunny/crossref_metadata_2025 huggingface dataset:
Meta-Analysis of the Research on Response Cards
Authors: Randolph Justus J.
Published: December 2007

In this meta-analysis, the author analyzed 18 response card articles, theses, or dissertations to determine the magnitude of effect that response card strategies have on test achievement, quiz achievement, class participation, and intervals of off-task behavior. The author also determined whether the type of response cards used or the presence or absence of ceiling effects had a differential effect on study outcomes. Using the traditional method of hand raising as a control condition, he found that response cards have large, statistically significant effect sizes for test achievement, quiz achievement, participation, and reduction in intervals of disruptive behavior. No significant difference was found between types of response cards used. Although the difference was not statistically significant, studies with ceiling effects had, on average, effect sizes that were notably lower than studies without ceiling effects. Place of publication, type of publication, and sample size were not significant moderators of effect sizes for academic achievement.
Social Engagement With Peers and Stereotypic Behavior of Children With Autism
Authors: Lee SoHyun , Odom Samuel L. , Loftin Rachel
Published: December 2007

In this study, the authors examined the relationship between engagement in social interaction with peers and stereotypic behavior. Three children with autism with relatively high rates of stereotypic behavior and low rates of social engagement with peers participated in the study. Two typically developing peers learned to direct social initiations to each participant during structured play activities, which increased the frequency of peer social engagement for the children with autism. Collateral decreases in stereotypic behavior occurred for all three participants when the peer-mediated intervention was implemented, and the results generalized to a proximal play setting. Conditional probability analyses further documented this inverse relationship between social and stereotypic behavior. Simultaneous (i.e., motor and oral/vocal) and motor stereotypic behaviors were the most directly affected by the increase in social engagement. Social validity ratings documented the social importance of the changes in both social engagement and stereotypic behavior for the children with autism.
Use of Brief Functional Analysis and Intervention Evaluation in Public Settings
Authors: Cihak David , Alberto Paul A. , Fredrick Laura D.
Published: December 2007

Educational experience in the community provides students with moderate and severe intellectual disabilities the opportunity to learn and rehearse skills they need to participate fully in community environments. The degree to which students with intellectual disabilities participate in their communities is often dependent on their ability to demonstrate appropriate behaviors when in public settings. For students with intellectual disabilities who exhibit socially inappropriate behavior, access to community programs may be limited or even denied. The purpose of this study was to investigate the identification and selection of interventions for inappropriate social behaviors maintained by negative reinforcement in public community settings. Four high school-age students with moderate to severe intellectual disabilities participated in a brief functional analysis to identify maintaining contingencies of target behaviors. Based on the resulting hypotheses, antecedent-based and response-based interventions were designed and compared. Results indicated that the antecedent-based intervention of self-operated auditory prompts worked as effectively as or better than the response-based intervention. In addition, teachers' social validity of intervention in public settings assessed the acceptability of both interventions. Teachers indicated that auditory prompts were socially acceptable for vocational training in public community settings.
Family Implementation of Positive Behavior Support for a Child With Autism
Authors: Lucyshyn Joseph M. , Albin Richard W. , Horner Robert H. , Mann Jane C. , Mann James A. , Wadsworth Gina
Published: December 2007

This study examined the efficacy, social validity, and durability of a positive behavior support (PBS) approach with the family of a girl with autism and severe problem behavior. The study was conducted across a 10-year period beginning when the child was 5 years old. A multiple baseline across family routines design evaluated the functional relationship between parent implementation of a PBS plan and longitudinal improvements in child behavior and successful participation in routines. Daily indicator behavior data allowed us to assess generalized improvements in child behavior. An inventory of monthly community activities allowed us to assess changes in child quality of life. In addition, social validity and contextual fit were assessed. Results document that the intervention was associated with a 75% reduction in problem behavior, and that the effects were maintained across a 6-month to 7-year follow-up period. Associated outcomes included generalized improvements in child behavior and enhanced community activity patterns. Parents also rated the social validity and contextual fit of the approach highly. Results verify the efficacy and social validity of the approach and offer preliminary descriptive evidence of its durability. Contributions to the literature, implications, and future directions are discussed.
A Picture Is Worth
Authors: Buggey Tom
Published: December 2007

Video self-modeling (VSM) is a relatively new technique for modifying and training behaviors and has accumulated a relatively impressive track record in the research literature. Using only positive examples, VSM gives persons the opportunity to view themselves performing a task just beyond their present functioning level via creative editing of videos using VCRs or video software. In this article, the author provides instructions on the two primary video-taping strategies for collecting content for self-modeling movies. These are accompanied by case studies illustrating the entire self-modeling process, from selecting behaviors to viewing the videos. The author conducted the case studies in his work with the Restructuring for Inclusive Environments technical assistance project. Suggested applications and caveats on the use of VSM are also presented.
Identifying Barriers and Facilitators in Implementing Schoolwide Positive Behavior Support
Authors: Kincaid Don , Childs Karen , Blase Karen A. , Wallace Frances
Published: December 2007

As the number of schools implementing systemic, schoolwide positive behavior support (PBS) processes expands (nationally, at least 5,000 schools are participating), increasing attention is being paid to the efficacy of implementation. This article describes a case study of the experiences of Florida's Positive Behavior Support Project, which used a systematic process to understand barriers and facilitators to the successful implementation of schoolwide positive behavior support by schools implementing at high and low levels of fidelity, and the degree to which the project could impact barriers and facilitators. Results indicate that schools implementing with low fidelity tend to identify practical, operational barriers, whereas schools implementing with high fidelity struggle with systems issues. Both high-implementing and low-implementing schools identified the same facilitators to implementation; however, they differed in their views of which facilitators the project could impact. Implications for state PBS project activities are discussed, along with suggestions for future data collection and providing a model of data-based decision making at a macro level.
Measuring School-wide Positive Behavior Support Implementation
Authors: Cohen Rachel , Kincaid Don , Childs Karen Elfner
Published: December 2007

School-wide positive behavior support (SWPBS) has been implemented in more than 4,000 schools as a means of addressing problem behavior in a systemic fashion. Preliminary outcomes (e.g., office discipline referrals, suspensions) indicate the effectiveness of SWPBS in decreasing school-wide behavior problems and creating a positive school climate. Although the results of a majority of the program evaluations yielded significant findings, there has been a lack of measurement of treatment fidelity, possibly due to the absence of expedient, effective assessment tools. This article describes the theoretical background and development, including a qualitative pilot study and psychometric properties, of the School-wide Benchmarks of Quality (BoQ; Kincaid, Childs, & George, 2005), a tool intended to measure the implementation of SWPBS. Descriptive data on the instrument, including internal consistency, test—retest reliability, interrater reliability, and concurrent validity, were collected and analyzed. Results indicate that the BoQ for SWPBS is a reliable, valid, efficient, and useful instrument for measuring the fidelity of implementation of the primary or universal level of PBS application in individual schools. Future considerations for evaluating the psychometric properties of the BoQ include extending the data collection and analysis to many more schools across multiple states.
Using Perseverative Interests to Elicit Joint Attention Behaviors in Young Children With Autism
Authors: Vismara Laurie A. , Lyons Gregory L.
Published: December 2007

Various explanations have been offered in the literature on the underlying cause of joint attention deficits in autism. One possible explanation is that children with autism are capable of producing joint attention but lack the social motivation to share their interests with others. The current study used a single-subject reversal design with alternating treatments to examine whether joint attention initiations for social sharing would occur as a collateral effect of utilizing the motivational techniques of Pivotal Response Treatment (PRT) in conjunction with perseverative interest stimuli for three young nonverbal children with autism. Results indicated an immediate increase in joint attention initiations when perseverative, or highly preferred, interests were incorporated within the motivational techniques of PRT. Additional findings included collateral increases in joint attention initiations toward less preferred interests, as well as improvements in the quality of interaction between the children and caregivers. Findings are discussed in terms of theoretical and clinical implications for understanding the role of motivation in the development of joint attention in autism.
Screening for Understanding
Authors: Lohrmann-O'Rourke Sharon , Knoster Tim , Llewellyn Gregory
Published: December 2007

Education teams have the responsibility for implementing the critical components of functional behavioral assessment (FBA) into practice. For many people who are unfamiliar with the assessment-intervention design process, the comprehensiveness of FBA can appear overwhelming. Teams need a practical and time-efficient starting point to begin gathering initial information about problem situations. Screening for Understanding of Student Problem Behavior: An Initial Line of Inquiry is one example of an initial information-gathering format for beginning a comprehensive FBA. This article illustrates the use of the Initial Line of Inquiry within school-based settings when using a team planning process for students engaging in challenging behavior. A case illustration demonstrates the process that guides application of the Initial Line of Inquiry, along with key questions and guiding thoughts pertinent to the design of effective behavioral support plans for focus students.
Self-Monitoring and Self-Recruited Praise
Authors: Todd Anne W. , Horner Robert H. , Sugai George
Published: December 2007

This study examines the relationship between self-monitoring plus self-recruited attention and problem behaviors, on-task behavior, overall teacher perception of student performance, task completion, and frequency of teacher praise. The research design employed an ABAB withdrawal analysis coupled with a two-series multiple baseline design across class periods for one fourth-grade student with learning disabilities and problem behavior in a general education classroom. The results indicate that implementation of self-monitoring combined with self-evaluation and self-recruitment of teacher attention was functionally related to a decrease in the frequency of problem behaviors, an increase in on-task behavior, and an increase in task completion. In addition, the intervention was associated with increased positive teacher perceptions of student performance. Results are discussed in terms of the application of (a) comprehensive, positive behavioral support in typical classrooms; (b) self management strategies to reduce problem behaviors; and (c) expanded research outcomes to document behavior change with social significance.
A Moral Framework for Analyzing the Controversy Over Aversive Behavioral Interventions for People with Severe Mental Retardation
Authors: Singer George H. S. , Gert Bernard , Koegel Robert L.
Published: December 2007

This article applies a systematic analysis of everyday moral decision making to the controversy surrounding the use of aversive treatments for people with severe mental retardation. The authors' aim is to provide a framework for analyzing the issue, and they take a position against the use of aversive procedures. The analysis adds some new ideas to the debate. It provides a definition of aversive procedures based upon common moral rules. The concept of protection by the moral rules is discussed and the case made that people with severe mental retardation deserve the protection of the moral rules and that this right is historically new and tenous. The importance of symbols of dehumanization is discussed in light of this tenous condition. The idea of moral agency is applied in order to clarify the kinds of societal sanctions that are and are not appropriate when a person with severe mental retardation violates a moral rule. The authors argue that data are always relevant to moral decision making and that a mounting body of evidence indicates that nonaversive alternatives are available and can replace aversive procedures in all but a very small number of highly unusual cases.
Functional Assessment Research on Students with or at Risk for EBD
Authors: Lane Kathleen L. , Umbreit John , Beebe-Frankenberger Margaret E.
Published: December 2007

The present article reports information resulting from a review of 19 articles reporting studies conducted in the 1990s with a total of 62 participants who were identified as having, or being at risk for, emotional and behavioral disorders (EBD). Studies were included in this review only if (a) a functional assessment was conducted, (b) the participants were identified as having, or being at risk for, EBD, and (c) the study was published after 1989. Findings indicate that functional assessment research is being conducted with young children in special and general education settings with the use of single-case design methodologies. A review is made of the nine articles that reported findings from functional assessment-based intervention studies. The review suggests that antecedent-based interventions, primarily curricular modifications, are most often examined. Results indicate that present research methodology includes important components essential to making valid conclusions from outcomes, and in generalizing findings. Directions for future research are discussed.
Teaching Parents of Children with Autism to Perform Functional Assessments to Plan Interventions for Extremely Disruptive Behaviors
Authors: Frea William D. , Hepburn Susan L.
Published: December 2007

Parents of children with autism often face unique challenges when attempting to understand and address their children's difficulty. Although professionals have used functional assessment to help design interventions that match the communicative intent of challenging behavior, parents often do not have this skill. This study investigated the ability of parents to learn the skills related to functional assessment and independently create interventions. The goals of the study were to (a) assess the ability of parents to use a manual in learning to perform a descriptive functional assessment, (b) identify whether the parents could generate functionally equivalent alternative behaviors, and (c) evaluate the parents' ability to independently teach the new behavior. Two families were assessed within controlled case studies. The results indicated that one family was immediately successful in utilizing functional assessment information to independently create an effective intervention, and the second family required a brief instructional session on prompting procedures to effectively implement the intervention.
Using Teacher-Implemented Instruction to Increase Language Intelligibility of Children with Autism
Authors: Smith Annette E. , Camarata Stephen
Published: December 2007

Abstract: This study examined the feasibility of an intervention using naturalistic language teaching procedures for communication problems of individuals with autism conducted by the child's general education teacher in collaboration with the child's language clinician. The results of a multiple baseline study across children indicate successful implementation of naturalistic language teaching procedures in the school settings by all general education teachers and improved intelligibility of the language skills of all the children with autism in generalized spontaneous language use. These results are discussed in terms of previous research demonstrating the effectiveness and benefits of naturalistic teaching procedures and in terms of the implications for educational practices involving children with autism.
Using Active Responding to Reduce Disruptive Behavior in a General Education Classroom
Authors: Armendariz Fernando , Umbreit John
Published: December 2007

Abstract: Active responding (in the form of response cards) was employed during a math lecture in a third-grade classroom to evaluate its effect on disruptive behavior. Two conditions, conventional lecture with hand raising and response cards, were alternated in a reversal (ABA) design. During baseline, the teacher used a conventional lecture with hand raising method, which consisted primarily of lecturing and then asking one child who had raised his or her hand to answer a question. During the active responding (response card) condition, all the students had to respond to the teacher's question by writing an answer on individual cards. Disruptive behavior decreased dramatically when the response cards were used and increased again when the conventional hand raising method was reinstated.
Training Responding Behaviors in Students with Autism
Authors: Buggey Tom , Toombs Kristina , Gardener Pia , Cervetti Michele
Published: December 2007

Videotaped self-modeling (VSM) has been developed as a means to allow participants to view themselves in situations where they are performing at a more advanced level than they typically function. VSM has been effectively used to train positive behaviors and to reduce unwanted behaviors across a range of ages and behaviors; however, studies of VSM have not been conducted with students with autism Our study was designed to analyze the effects of VSM on the acquisition and maintenance of appropriate verbal responses to questions by children with autism. A multiple baseline design across students was used to evaluate performance. The results indicated that the three participants almost doubled their rates of appropriate responding to questions during play situations. The findings suggest that VSM may constitute a positive behavior change intervention worthy of consideration in a treatment regimen.
Educational Inclusion of Children with Severe Disabilities
Authors: Harrower Joshua K.
Published: December 2007

The educational inclusion of children with disabilities has long been a topic of controversy. In this article the relevant research literature is reviewed in order to present a rationale for the educational inclusion of children with disabilities, a summary of the effects of inclusive placement on the social and academic performance of children with and without disabilities, a summary of the research exploring the impact of educators and parents on the process of inclusion, and an evaluation of recent approaches for facilitating the educational inclusion of children with disabilities.
Increasing Homework Completion by Incorporating Student Interests
Authors: Hinton L. Michelle , Kern Lee
Published: December 2007

Incorporating topics of student interest into nonpreferred academic activities is a strategy that has been used successfully to increase engagement and decrease problematic behavior. In the current study, we included topics of student interest in homework assignments. The intervention was applied across a middle school classroom of fifth-grade students. During baseline, homework completion averaged approximately 60%. After incorporating student interests into assignments, homework completion increased to over 95%. The effects were replicated using a reversal design, with similar percentages of homework completion.
Family-Centered, Assessment-Based Intervention to Improve Behavior During an Early Morning Routine
Authors: Clarke Shelley , Dunlap Glen , Vaughn Bobbie
Published: December 2007

This article presents a demonstration of assessment-based intervention conducted in a family context to improve the responding of a boy with Asperger syndrome during the early morning routine of getting dressed and ready for school. Following a process of functional assessment, we developed a multicomponent intervention package, which was implemented by the boy's mother. We used a reversal design to demonstrate the effectiveness of the intervention package. The results showed that the intervention produced a substantial reduction of problem behaviors, higher levels of on-task responding, and a clear decrease in the length of time required to complete the morning routine. This empirical analysis provides another demonstration of the efficacy of a family-centered approach of assessment-based positive interventions in natural family contexts.
The Abu Ghraib torture photographs
Authors: Andén-Papadopoulos Kari
Published: December 2007

Drawing on a close analysis of how the Abu Ghraib photographs originally were perceived and framed in the American news media, public debate, and in various cultural contexts, this article addresses the question of how iconic news media images exercise power in the shaping of news, politics, and public opinion. It specifically takes issue with the tendency among prominent communication scholars to assume that visuals mainly function to support dominant news frames and elite political discourse with little or no potential for independent influence on audiences. The key conclusion of the article is that the Abu Ghraib photographs were not in any simple way `spoken for' or tamed by the dominant news frames, but quite the opposite. The photographs have themselves come to function as a critical prism through which elite and popular views on US foreign policy are refracted, in the sense that the heretofore banned sight of American troops in the role of sadistic torturers has become an integral part of our understanding of the Bush administration's `war on terror'. The impact of these photographs is not least suggested by their proliferation in the wider culture, where they, through various creative and counter-framing practices, often have been transformed into sites of protest and opposition to the very deeds they represent.
The contribution of online news consumption to critical-reflective journalism professionals
Authors: Spyridou Paschalia-Lia , Veglis Andreas
Published: December 2007

Evidence suggests that the internet is the medium with the most success in attracting young people to news, while traditional media have been facing increasing trouble since the 1980s. The emergence of cynical and sceptical attitudes about politics and the media has resulted in most young people becoming `news grazers' instead of regular news consumers. Journalism students, however, should be exposed to political information not only as part of their civic obligation, but also in order to be fully equipped to make essential contributions as future analysts and brokers of news. By proposing a conceptual approach on how online news consumption contributes to critical reflective journalism, and drawing upon informed citizenry theory, the knowledge gap hypothesis, the diffusion of innovations model and the uses and gratification perspective, this article attempts to investigate the determinants and consumption patterns of online news by journalists-to-be in Greece. It is argued that conventional predictors such as possession of substantial cultural capital and longer surfing hours have supremacy over the perceived utility of self-education, job experience and simulation.
'Collective memory': A memoir and prospect
Authors: Olick Jeffrey K.
Published: December 2007

This article reflects on the past, present and future states of social memory studies. Despite the proliferation of work employing the term `collective memory', the field retains the `non-paradigmatic, transdisciplinary, centerless' qualities identified in 1998. As a result, this essay celebrates the appearance of Memory Studies along with a number of other endeavors promising systematization and institutionalization in the vast literature on social memory.
Memory studies: For and against
Authors: Radstone Susannah
Published: December 2007

This article examines the opportunities and risks afforded by the consolidation of memory research into the subject area of `memory studies'. Debates about memory culture outside the academy and within academic memory research have hinged on its perceived over-personalization of the political. However, memory research is often informed by a broader ethical turn that understands itself to be transforming politics. The article argues that this split results in part from the over-generalizations produced by the travelling concepts of a transdisciplinary memory studies. It concludes that the politics of memory culture and of memory research might be best analysed and practiced within the disciplines and by means of the research methods from which memory studies borrows.
Remembering and reminiscing: How individual lives are constructed in family narratives
Authors: Fivush Robyn
Published: December 2007

Stories we tell about our lives very much define who we are as individuals, within particular families, cultures and historical periods. In this article, I review psychological research that demonstrates how autobiographical memories are created and re-created in daily interactions in which we share our stories with others, and how this process is modulated by individual, gendered and cultural models of self expressed in everyday family reminiscing. I focus on two critical developmental periods: the preschool years when autobiography is just beginning to emerge; and adolescence when autobiographical memories begin to coalesce into an overarching life narrative that defines self, others and values. I show how individual differences in the ways in which families reminisce are related to individual autobiographical narratives. Importantly, just as our individual narratives are shaped by cultural and historical models of selves and lives, individuals come to shape their culture and their historical moment by the stories they tell.
Memory, consumerism and media: Reflections on the emergence of the field
Authors: Sturken Marita
Published: December 2007

This article situates the emergence of the field of memory studies in relation to several areas of study: cultural studies, media studies, communication and visual culture. It considers key concepts of those fields — memory practices, technologies of memory, mediation and consumerism — in relation to memory studies. Finally, it reflects on some cautionary aspects of memory studies as it moves forward as a field of study.
Why memory's work on journalism does not reflect journalism's work on memory
Authors: Zelizer Barbie
Published: December 2007

This article discusses the symbiotic, though uneven, relationship linking scholarship on journalism and memory. Though work on collective memory has yet to recognize the centrality of journalism as an institution of mnemonic record, memory creeps into journalistic relay so often that it renders journalism's memory work both widespread and multi-faceted. This renders journalism a key agent of memory work, even if journalists themselves are averse to admitting it as part of what they do and even if memory scholars have not yet given journalism its due.
Divided pasts: A premature memorial and the dynamics of collective remembrance
Authors: Rigney Ann
Published: December 2007

The commemoration of the participation of Irishmen in the British army in the first World War has reflected the political divisions on the island. This article focuses on the Irish National War Memorial, which was built in the 1930s in Dublin but only officially opened in the 1990s, and analyses the cultural life of this monument in relation to the difficult integration of a marginalized group into the dominant national narrative. The case is used to support a call for an integrated study of collective remembrance that takes into account both its multi-medial character and the dynamic interplay between cultural and social processes.
Gene alteration and precursor and mature microRNA transcription changes contribute to the miRNA signature of primary effusion lymphoma
Authors: O'Hara Andrea J. , Vahrson Wolfgang , Dittmer Dirk P.
Published: December 2007

MicroRNAs are regulated by gene alteration, transcription, and processing. Thus far, few studies have simultaneously assessed all 3 levels of regulation. Using real-time quantitative polymerase chain reaction (QPCR)–based arrays, we determined changes in gene copy number, pre-miRNA, and mature miRNA levels for the largest set of primary effusion lymphomas (PELs) to date. We detected PEL-specific miRNA gene amplifications, and concordant changes in pre-miRNA and mature miRNA. We identified 68 PEL-specific miRNAs. This defines the miRNA signature of PEL and shows that transcriptional regulation of pre-miRNA as well as mature miRNA levels contribute nonredundant information that can be used for the classification of human tumors.
Characterisation of mycobacteria isolated from slaughter cattle in pastoral regions of Uganda
Authors: Oloya J , Kazwala R , Lund A , Opuda-Asibo J , Demelash B , Skjerve E , Johansen TB , Djønne B
Published: December 2007

Background

Bovine tuberculosis is a zoonotic problem in pastoral cattle and communities in Uganda. Tuberculin tests in pastoral cattle had shown a high herd but low animal prevalence, with a high proportion of avian reactors. No work had been done to identify the mycobacterial species involved. The objective of the study was to isolate and characterise Mycobacterial species causing tuberculous lesions in slaughtered animals. Lesioned organs compatible with bovine tuberculosis in slaughtered cattle from pastoral areas in Uganda were collected and cultured to isolate mycobacteria. AccuProbe culture identification kits for the Mycobacterium tuberculosis complex, M. avium complex and M. avium were used to identify the isolates. Spoligotyping and Insertion Sequence (IS) 1311 and IS1245 Restriction Fragment Length Polymorphism analysis (RFLP) were used to further characterise the isolates.

Results

Of the 61 lesioned organs and tissues cultured, 19 isolates were identified as M. bovis, 3 as M. avium subsp.hominissuis, 1 as M. intracellulare, 1 as a mixed culture of M. bovis and M. avium sp. and 1 as M. avium sp. and unidentified mycobacteria. Eleven other mycobacteria outside the tuberculosis and avium complex groups were also isolated. Ten new spoligopatterns grouped into three clusters were identified from M. bovis isolates. Two of the three M. avium subsp.hominissuis isolates showed similar patterns on the IS1311 RFLP but all were different on the IS1245 RFLP.

Conclusion

The isolation of M. bovis confirms the ongoing infection with spoligotypes unique to Uganda. Isolation of environmental mycobacteria could explain the high avian or non specific tuberculin reactor patterns commonly observed in pastoral cattle and suggests their pathogenic or opportunistic role in the infection of cattle with disseminated bovine tuberculous lesions.
Direct selection and phage display of a Gram-positive secretome
Authors: Jankovic Dragana , Collett Michael A , Lubbers Mark W , Rakonjac Jasna
Published: December 2007

Surface, secreted and transmembrane protein-encoding open reading frames, collectively the secretome, can be identified in bacterial genome sequences using bioinformatics. However, functional analysis of translated secretomes is possible only if many secretome proteins are expressed and purified individually. We have now developed and applied a phage display system for direct selection, identification, expression and purification of bacterial secretome proteins.
Loss of function in virus-specific lung effector T cells is independent of infection
Authors: Arimilli Subhashini , Palmer Ellen M , Alexander-Miller Martha A
Published: December 2007

Recently, several studies, including those with respiratory syncytial virus, mouse pneumovirus, and simian virus 5, have reported that virus-specific CD8+ effector cells entering the lung as a result of respiratory infection undergo significant loss of function. The impaired function in these cells has been proposed to be the result of infection-induced changes in the lung. Although virus-specific effects may contribute to regulation of T cells in the lung, the findings from this study provide evidence that the basal lung environment is sufficient to promote loss of function in effector cells. Loss of function occurs within 48 h of entry into the lung and is most evident in cells residing in the lung parenchyma. These findings suggest an additional paradigm for the immunoregulation of effector cells that enter the lung as a result of virus infection.
Posttranslational Regulation of Bim by Caspase‐3
Authors: WAKEYAMA HIDETOSHI , AKIYAMA TORU , KADONO YUHO , NAKAMURA MASAKI , OSHIMA YASUSHI , NAKAMURA KOZO , TANAKA SAKAE
Published: December 2007

Abstract:  Bim is a proapoptotic BH3‐domain‐only member of the Bcl‐2 family, and its expression is regulated both transcriptionally and posttranslationally. We developed an in vitro system examining the posttranslational regulation of Bim. Since Bim is a strong mediator of apoptosis, it has been quite difficult to establish cell lines stably overexpressing Bim. Coexpression of Bcl‐2 enabled us to obtain mouse embryonic fibroblasts (MEFs) in which Bim is overexpressed and Bcl‐2 expression is regulated by Tet‐off system. Reduction of Bcl‐2 levels by doxycycline treatment induced caspase‐3 and caspase‐7 activation, which was followed by Bim degradation. Bim degradation was suppressed by gene knockdown of caspase‐3, but not by caspase‐7 knockdown. The same posttranslational regulation of Bim was observed in osteoclasts. These results suggest that caspase‐3 negatively regulates Bim expression by stimulating its degradation, thus creating a negative feedback loop in the Bim–caspase axis.
A Chromosomal Inversion within a Quantitative Trait Locus Has a Major Effect on Adipogenesis and Osteoblastogenesis
Authors: ACKERT‐BICKNELL CHERYL L. , SALISBURY JESSE L. , HOROWITZ MARK , DeMAMBRO VICTORIA E. , HORTON LINDSAY G. , SHULTZ KATHRYN L. , LECKA‐CZERNIK BEATA , ROSEN CLIFFORD J.
Published: December 2007

Abstract:  We mapped a quantitative trait locus (QTL) for BMD to mid‐distal chromosome (Chr) 6 in a cross between C57BL/6J (B6) and C3H/HeJ (C3H). The B6.C3H‐6T (6T) congenic was developed to map candidate genes in this QTL. Recently, a 25 cM paracentric inversion was discovered on Chr 6 in C3H/HeJ; we found 6T also carries this inversion. Microarrays from the liver of B6 and 6T uncovered two narrow bands of decreased gene expression in close proximity to the predicted locations of the inversion breakpoints. Changes in specific gene expression in 6T were consistent with its phenotype of low trabecular bone volume and marrow adipogenesis. The BXH recombinant inbred (RI) strains do not carry the C3H/HeJ inversion. To test if the inversion, or allelic effects, were responsible for the 6T phenotype, we made a new congenic, B.H‐6, developed by introgressing a 30 Mb region of C3H genomic sequence from BXH6 onto a B6 background. While genetically identical to 6T, this new congenic had a distinct metabolic and skeletal phenotype, with more body fat and greater trabecular BV/TV compared to B6 or 6T. We conclude that the phenotype of 6Tcannot be explained by simple allelic differences in one or more genes from C3H. Rather, 6T demonstrates that disordered regulation of gene expression by genomic rearrangement can have a profound effect on a complex trait, such as BMD, and that genomic rearrangement can supersede the effects of various alleles.
Correlation among Hyperphosphatemia, Type II Sodium–Phosphate Transporter Activity, and Vitamin D Metabolism in Fgf‐23 Null Mice
Authors: SITARA DESPINA
Published: December 2007

Abstract:  Phosphate homeostasis is mostly regulated through humoral factors exerting direct or indirect effects on transporter proteins located in the intestine and kidney. Fibroblast growth factor 23 (FGF‐23) is a major phosphate‐regulating molecule, which can affect both renal and intestinal phosphate uptake to influence overall mineral ion homeostasis. We have found that Fgf‐23 gene knockout mice (Fgf‐23−/−) develop hyperphosphatemia that consequently leads to abnormal bone mineralization, and severe soft tissue calcifications. On the contrary, FGF‐23 transgenic mice develop hypophosphatemia and produce rickets‐like features in the mutant bone. Further studies using our Fgf‐23−/− mice have identified an inverse correlation between Fgf‐23, and vitamin D or NaPi2a; genomic elimination of either vitamin D or NaPi2a activities from Fgf‐23−/− mice could reverse severe hyperphosphatemia to hypophosphatemia, and consequently could alter skeletal mineralization, suggesting that regulation of phosphate homeostasis in Fgf‐23−/− mice is vitamin D‐ and NaPi2a‐mediated process.
Tumor Necrosis Factor Family Receptors Regulating Bone Turnover
Authors: ROBINSON LISA J. , BORYSENKO CHRISTOPHER W. , BLAIR HARRY C.
Published: December 2007

Abstract:  While the tumor necrosis factor (TNF) family members RANKL and TNF‐α are critical regulators of osteoclast formation, functions of other TNFs in bone are poorly understood. Here we consider the roles in regulating bone turnover of TNF receptors (TNF‐R) also expressed by osteoblasts and osteoblast precursors. TNF receptors in osteoblasts and preosteoblasts include TNFR1 (p55), DR3 (TNFR25), DR5 (TRAIL‐R2) and Fas, and possibly FN14 and DR4 (TRAIL‐R1). Osteoblasts also produce soluble TNF receptors, DcR2, osteoprotegerin, and sDR3; these bind the TNFs TRAIL, RANKL, TL1A, and Apo3L and block ligand effects on cell surface receptors. Activation of DR3 regulates osteoblast maturation and may control the decision to exit the pool of differentiation‐competent preosteoblasts. A major natural ligand for DR3, TL1A, is produced by vascular cells adjacent to differentiating osteoblasts and possibly by Fcγ‐stimulated osteoclast precursors. The activity of DR3 is regulated by osteoblast production of its soluble DR3 splice variant. Activation of TNFR1 or DR5 by TNF‐α or TRAIL may regulate osteoblast connectivity, which is important to bone turnover. When there is a source for Fas ligand, such as an inflammatory infiltrate, activation of Fas may lead to apoptosis of any bone cell. TNF receptors are thus implicated in multiple aspects of bone turnover.
Balanced Regulation of Proliferation, Growth, Differentiation, and Degradation in Skeletal Cells
Authors: BLAIR HARRY C. , SUN LI , KOHANSKI RONALD A.
Published: December 2007

Abstract:  In cartilage and bone‐producing cells, proliferation and growth are balanced with terminal differentiation. Maintaining this balance is essential for modeling, growth, and maintenance of the skeleton. Cartilage growth follows a program regulated by hormones and cytokines interacting with a counter‐regulatory system in which hedgehog and parathyroid hormone (PTH)‐rP signals are key elements. This maintains chondrocyte proliferation and, at specific sites, allows differentiation. Bone is produced by differentiation of mesenchymal stem cells on a scaffold of mineralizing cartilage. However, bone, once formed, is continually resorbed and replaced. Thus, maintenance of bone mass requires retention of stem cells and preosteoblasts in undifferentiated division‐competent stages. Maintenance of the undifferentiated states is poorly understood, whereas the rate of osteoblast formation is regulated in part by PTH and insulin‐like growth factor. The precursor pool is also subject to depletion by differentiation of mesenchymal stem cells to nonbone cells including adipocytes. In the aging skeleton, disordered balance between bone formation and resorption is in major part due to immune dysregulation that increases formation of bone‐degrading osteoclasts; tumor necrosis factor (TNF)‐α is a major intermediate in this process.
Genetics of Hypercalciuric Nephrolithiasis
Authors: STECHMAN MICHAEL J. , LOH NELLIE Y. , THAKKER RAJESH V.
Published: December 2007

Abstract:  Renal stone disease (nephrolithiasis) affects 5% of adults and is often associated with hypercalciuria. Hypercalciuric nephrolithiasis is a familial disorder in more than 35% of patients, and may occur as a monogenic disorder, or as a polygenic trait involving 3 to 5 susceptibility loci in man and rat, respectively. Studies of monogenic forms of hypercalciuric nephrolithiasis in man, for example, Bartter syndrome, Dent's disease, autosomal dominant hypocalcemic hypercalciuria (ADHH), hypercalciuric nephrolithiasis with hypophosphatemia, and familial hypomagnesemia with hypercalciuria have helped to identify a number of transporters, channels, and receptors that are involved in regulating the renal tubular reabsorption of calcium. Thus, Bartter syndrome, an autosomal recessive disease, is caused by mutations of the bumetanide‐sensitive Na‐K‐Cl (NKCC2) cotransporter, the renal outer‐medullary potassium channel (ROMK), the voltage‐gated chloride channel, CLC‐Kb, or in its β subunit, Barttin. Dent's disease, an X‐linked disorder characterized by low molecular weight proteinuria, hypercalciuria, and nephrolithiasis, is due to mutations of the chloride/proton antiporter, CLC‐5; ADHH is associated with activating mutations of the calcium‐sensing receptor, which is a G protein‐coupled receptor; hypophosphatemic hypercalciuric nephrolithiasis associated with rickets is due to mutations in the type 2c sodium–phosphate cotransporter (NPT2c); and familial hypomagnesemia with hypercalciuria is due to mutations of paracellin‐1, which is a member of the claudin family of membrane proteins that form the intercellular tight junction barrier in a variety of epithelia. These studies have provided valuable insights into the renal tubular pathways that regulate calcium reabsorption and predispose to kidney stones and bone disease.
Suppression of PPAR Transactivation Switches Cell Fate of Bone Marrow Stem Cells from Adipocytes into Osteoblasts
Authors: TAKADA ICHIRO , SUZAWA MIYUKI , MATSUMOTO KUNIHIRO , KATO SHIGEAKI
Published: December 2007

Abstract:  Osteoblasts and adipocytes differentiate from common pleiotropic mesenchymal stem cells under transcriptional controls by numerous factors and multiple intracellular signalings. However, cellular signaling factors that determine cell fates of mensenchymal stem cells in bone marrow remain to be largely uncovered, though peroxisome proliferator‐activated receptor‐γ (PPAR‐γ) is well established as a prime inducer of adipogenesis. Here, we describe two signaling pathways that induce the cell fate decision into osteoblasts from adipocytes. One signaling is a TAK1/TAB1/NIK cascade activated by TNF‐α and IL‐1, and the activated NF‐κB blocked the DNA binding of PPAR‐γ, attenuating the activated PPAR‐mediated adipogenesis. The second signaling is the noncanonical Wnt pathway through CaMKII‐TAK1/TAB2‐NLK. Activated NLK by a noncanonical Wnt ligand (Wnt‐5a) transrepresses PPAR transactivation through a histone methyltransferase, SETDB1. Wnt‐5a induces phosphorylation of NLK, leading to the formation of a corepressor complex that inactivates PPAR function through histone H3‐K9 methylation. Thus, two signaling pathways lead to an osteoblastic cell lineage decision from mesenchymal stem cells through two distinct modes of PPAR transrepression.
Nuclear Receptors and Bone
Authors: MARGOLIS RONALD N.
Published: December 2007

Abstract:  Nuclear receptors (NRs) represent a class of ligand‐dependent and ‐independent transcription factors with importance to the regulation of development, reproduction, and metabolism. The emergence of new understanding of the structure, function, and role in disease of NRs provides new insights into the interaction between genetics and the environment, with NRs representing new targets for the development of therapeutic agents. NRs play key roles in bone health and contribute to our understanding of diseases and disorders that result in osteopenia and osteoporosis. The Nuclear Receptor Signaling Atlas (http://www.nursa.org) is an online repository of information about NRs and provides a community‐wide resource designed to help catalyze new advances in biology and medicine.
Cellular and Molecular Consequences of Calcineurin Aα Gene Deletion
Authors: SUN LI , ZHU LING‐LING , ZAIDI NEEHA , YANG GUOZHE , MOONGA BALJIT S. , ABE ETSUKO , IQBAL JAMEEL , EPSTEIN SOLOMON , BLAIR HARRY C. , HUANG CHRISTOPHER L.‐H. , ZAIDI MONE
Published: December 2007

Abstract:  Here we briefly review our studies that have unraveled an important role for the calcium‐ and calmodulin‐sensitive enzyme calcineurin (CN) in bone remodeling. We find that the genetic deletion of the calcineurin Aα isoform results in osteoporosis, which is recapitulated in humans following calcineurin inhibitor therapy widely used after solid organ transplantation. Mechanistically, however, while both calcineurin inhibitors cyclosporine and tacrolimus initially stimulate osteoclastic bone resorption in humans, the predominant feature in the CNAα null mouse is a profound reduction in bone formation. We speculate that the so‐called “calcineurin inhibitors” may interact with molecules other than calcineurin. The clinical relevance of these observations is explored.
Multiplicity of BMP Signaling in Skeletal Development
Authors: WU XIANGWEI , SHI WEIBIN , CAO XU
Published: December 2007

Abstract:  Skeletal development and homeostasis are complex processes involving systemic regulatory factors and local factors present in the bone microenvironment. Among these factors, bone morphogenetic proteins (BMPs) represent the major potent bone morphogens, which coordinate with other factors to exert their multiple functions by regulating cell condensation, as well as inducing chondrogenesis and osteogenesis. This article reviews the current status of BMP signaling in skeletal development, with focus on regulation at the level of the receptors. Crosstalk of the BMP pathway with other major signaling pathways is also summarized.