bluuebunny/crossref_metadata_2025 huggingface dataset:
Homozygous Myotonic Dystrophy With Craniosynostosis
Authors: Cerghet Mirela , Tapos Daniela , Serajee Fatema J. , Mahbubul Huq A. H. M.
Published: May 2008

Myotonic dystrophy is considered a true dominant condition with no difference in the phenotype between heterozygous and homozygous cases. The homozygous state is very rare and only a few patients have been reported in the literature. We report a 2.5-year-old boy from a nonconsanguineous marriage, with a unique combination of clinical and radiological findings: hypotonia, motor and language developmental delay, ventriculomegaly, subcortical white matter lesions, and craniosynostosis. Mutation analysis revealed 2 copies of expansion mutation of 1260 and 60 cytosine-thymine-guanine repeats in the myotonic dystrophy protein kinase gene. Both the mildly symptomatic (434 repeats) mother and the asymptomatic (37 repeats) father are heterozygous. Craniosynostosis has not been reported previously in myotonic dystrophy. This homozygous case expands the clinical spectrum of myotonic dystrophy type 1 and provides support to the hypothesis that myotonic dystrophy type 1 pathophysiology could be, in part, due to the loss of normal function of the wild-type protein.
Cryptogenic Stroke in a Boy With Atrial Septal Defect and Hyperhomocysteinemia
Authors: Indolfi Giuseppe , Bartolini Elisa , Trapani Sandra , Azzari Chiara , Resti Massimo
Published: May 2008

In children, clinical recognition of stroke and determination of its exact etiology are extremely difficult. The authors described a case of cryptogenic stroke in a 14-year-old-boy with asymptomatic atrial septal defect and hypercoagulable state. Paradoxical embolism was hypothesized as the responsible etiopathological mechanism. It is crucial to increase clinician awareness of stroke in children.
Quality of Life and Seizure Outcome After Vagus Nerve Stimulation in Children With Intractable Epilepsy
Authors: Sherman Elisabeth M. S. , Connolly Mary B. , Slick Daniel J. , Eyrl Kim L. , Steinbok Paul , Farrell Kevin
Published: May 2008

This study examined the effect of vagus nerve stimulation on quality of life in children with epilepsy using a validated quality-of-life scale and an empirical technique that accounts for measurement error in assessing individual change (the reliable change index). Participants were 34 children with severe intractable epilepsy who underwent vagus nerve stimulation and 19 children with intractable epilepsy who received medical management. Parent-completed epilepsy-specific and global ratings at baseline and after 1 year indicated that most children had no changes in quality of life following vagus nerve stimulation (52%-77%), similar to the comparison group. There was a trend for decreases to be less common in the vagus nerve stimulation group (14% vs 37%, P < .07), but there was no relation between improved quality of life and seizure control. The results raise questions about the mechanisms that underlie changes in quality of life after vagus nerve stimulation in this group of children.
Leucoencephalopathy, Transverse Myelopathy, and Peripheral Neuropathy in Association With Glutamic Acid Decarboxylase-65 (GAD) Antibodies in Children With Cancer
Authors: Ledet Davonna S. , Handgretinger Rupert , Bertorini Tulio E. , Hale Gregory A. , Ribeiro Raul C. , Khan Raja B.
Published: May 2008

Neurologic toxicity may occur as a direct effect of cancer and its therapy or indirectly because of a dysfunctional immune system. The authors report the development of axonal neuropathy, myelopathy, and leucoencephalopathy associated with glutamic acid decarboxylase-65 (GAD) antibodies in 4 children with progressive cancer who were heavily pretreated. Three patients with refractory leukemia and 1 with Ewing sarcoma developed paraplegia with sensory level and dorsal column dysfunction. Three developed leucoencephalopathy and 1 died of neurologic disease. All had high serum titers of GAD antibodies during the progressive phase of the illness, and the antibody levels returned to normal with the stability of the neurologic disease. Three survivors are showing gradual recovery. This syndrome of central and peripheral nervous system toxicity may have resulted from chemotherapy toxicity or from immune dysfunction, as suggested by the high GAD antibody titers.
Designing Communities to Enhance the Safety and Mobility of Older Adults
Authors: Dumbaugh Eric
Published: May 2008

By 2030, seventy-two million people, or fully one of every five Americans, will be aged sixty-five or older, raising important concerns about how our cities, communities, and transportation facilities will safety accommodate their travel needs. The current policy solution is to increase driver testing, provide senior-oriented paratransit services, and ultimately, to house older, nondriving adults in senior care communities where more mobile individuals can provide basic household-related services for them. These practices, while perhaps well intentioned, effectively segregate older adults from the larger community. We can do better. This article summarizes the available literature on the travel-related needs, abilities, and preferences of older adults. Through a synthesis of the current knowledge, it identifies four strategies that can be used to design communities and transportation systems to address the safety and mobility needs of an aging population in an inclusive, universal manner.
Forecasting Interest Rates in India
Authors: Dua Pami , Raje Nishita , Sahoo Satyananda
Published: May 2008

This paper develops univariate (ARIMA and ARCH/GARCH) and multivariate models (VAR, VECM and Bayesian VAR) to forecast short- and long-term rates, viz., call money rate, 15–91 days Treasury Bill rates and interest rates on Government securities with (residual) maturities of one year, five years and 10 years. Multivariate models consider factors such as liquidity, repo rate, yield spread, inflation rate, foreign interest rates and forward premium. The paper finds that multivariate models generally outperform univariate ones over longer forecast horizons. Overall, the paper concludes that the forecasting performance of Bayesian VAR models is satisfactory for most interest rates and their superiority in performance is marked at longer forecast horizons.
Directions for a Troubled Discipline
Authors: Jarzabkowski Paula , Whittington Richard
Published: May 2008

This Dialog responds to a growing debate about the relevance of business schools generally and the value of strategy theory and research for strategic management practice. The authors propose that academic theory and management practice can be better connected through management education. The academy researches practice, derives theory, and returns it to practice through the development of teaching materials and the teaching of current and future practitioners. The three articles in this Dialog examine how different approaches to strategy research inform strategy teaching and its application to practice. Joseph Bower explains the rise of business policy and the process research approach that informed that teaching tradition at Harvard Business School. Robert Grant responds by emphasizing the economic theory underpinnings of strategic management research and its impact on teaching. Paula Jarzabkowski and Richard Whittington conclude by proposing a strategy-as-practice perspective and suggesting ways to better incorporate strategy-as-practice research into strategy teaching.
On the importance of intellectual property rights for e-science and the integrated health record
Authors: D'Agostino Giuseppina , Hinds Chris , Jirotka Marina , Meyer Charles , Piper Tina , Rahman Mustafizur , Vaver David
Published: May 2008

An integrated health record (IHR) that enables clinical data to be shared at a national level has profound implications for medical research. Data that have been useful primarily within a single clinic will instead be free to move rapidly around a national network infrastructure. This raises challenges for technologists, clinical practice, and for the governance of these data. This article considers one specific issue that is currently poorly understood: how intellectual property (IP) relates to the sharing of medical data for research on large-scale electronic networks. Based on an understanding of current practices, this article presents recommendations for the governance of IP in an integrated health record.
Reconfiguring the health supplier market: changing relationships in the primary care supplier market in England
Authors: Sugden Bob , Wilson Rob , Cornford James
Published: May 2008

The multi-billion NHS Connecting for Health programme in England has completely reconfigured the relationships between the Department of Health, the National Health Service (NHS), primary care computing suppliers and healthcare professionals (including general practitioners). The implications of this reconfiguration are now becoming apparent and have potentially significant effects on the delivery of information and information systems in the health context. This article explores the changes in these relationships by drawing on comparisons with the previous system for procurement of primary care computing systems, which ran for much of the 1990s. The article also comments on characteristics of the CfH procurement/ contracting process, the differing responses of suppliers, and the role of the existing installed base as an actor in building a new infrastructure for health records.
The challenging nature of patient identifiers: an ethnographic study of patient identification at a London walk-in centre
Authors: Lichtner Valentina , Wilson Stephanie , Galliers Julia R.
Published: May 2008

The correct identification of a patient's health record is the foundation of any safe patient record system. There is no building of a `patient history', no sharing or integration of a patient's data without the retrieval and matching of existing records. Yet there can often be errors in this process and these may remain invisible until a safety incident occurs. This article presents the findings of an ethnographic study of patient identification at a walk-in centre in the UK. We offer a view of patient identifiers as used in practice and show how seemingly simple data, such as a person's name or date of birth, are more complex than they may at first appear and how they potentially pose problems for the use of integrated health records. We further report and discuss a dichotomy between the identifiers needed to access health records and the identifiers used by practitioners in their everyday work.
The Spread of Security Communities: Communities of Practice, Self-Restraint, and NATO's Post—Cold War Transformation
Authors: Adler Emanuel
Published: May 2008

This article invokes a combination of analytical and normative arguments that highlight the leading role of practices in explaining the expansion of security communities. The analytical argument is that collective meanings, on which peaceful change is based, cognitively evolve — i.e. they are established in individuals' expectations and dispositions and they are institutionalized in practice — because of communities of practice. By that we mean like-minded groups of practitioners who are bound, both informally and contextually, by a shared interest in learning and applying a common practice. The normative argument is that security communities rest in part on the sharing of rational and moral expectations and dispositions of self-restraint. This thesis is illustrated by the example of the successful expansion of security-community identities from a core of North Atlantic Treaty Organization (NATO) states to Central and Eastern European countries during the 1990s, which was facilitated by a `cooperative-security' community of practice that, emerging from the Helsinki Process, endowed NATO with the practices necessary for the spread of self-restraint.
Norms, Strategies and Political Change: Explaining the Establishment of the Convention on the Future of Europe
Authors: Dimitrakopoulos Dionyssis
Published: May 2008

Norms affect political outcomes by shaping the strategies that political actors use to advance their interests. Norms do so by shaping the terms of the debates that underpin political decision making. Unlike existing literature that highlights the importance of persuasion, this article demonstrates that through the mechanism of rhetorical action, norms induce self-interested political actors to adapt their strategy and accept political change that they would normally oppose. The case of the advent of the Convention on the Future of Europe examined here shows that by considering the impact of norms on the behaviour of the opponents of change, ideational analyses can incorporate agency in the explanation of political change.
Recognition and Collective Identity Formation in International Politics
Authors: Greenhill Brian
Published: May 2008

Applying the model of `recognition politics' to international relations can help to explain the identity-based elements of international conflicts that rationalist models leave out. This article uses psychological theories of identity formation to critically assess the recent move by constructivist scholars (most notably Alexander Wendt) to bring the Hegelian idea of the `struggle for recognition' into the study of IR. Examining recognition theory in this way shows that while the insights of `identity theory' developed in the symbolic interactionist tradition lend support to the idea that recognition of the `other' is essential to constituting the identity of the `self', much of the experimental work carried out within Social Identity Theory and its related fields fails to support the claim that recognition leads to the formation of an over-arching collective identity. Without a credible mechanism for collective identity formation, recognition theory fails to predict fundamental change in the international system.
Trends in leisure time physical activity among young people in Finland, 1977—2007
Authors: Laakso Lauri , Telama Risto , Nupponen Heimo , Rimpelä Arja , Pere Lasse
Published: May 2008

The decline in physical activity among young people has been discussed in the media during recent decades, although the scientific evidence for this has been scarce. The aim of this study was to investigate trends over 30 years in leisure time physical activity of Finnish boys and girls aged 12, 14, 16 and 18 years from 1977 to 2007. The data were obtained from the Finnish Adolescent Health and Lifestyle Survey. In the survey nationwide samples have been drawn every second year (number of respondents has varied from 2832 to 8390) since 1977. Leisure time physical activity was measured through questions concerning organized sport and unorganized leisure time physical activity. Participation in organized sport significantly increased from 1977 to 2007 in both genders. Time × gender interaction was significant, indicating that participation had increased more among girls than among boys. In both genders participation in unorganized leisure time physical activity decreased from 1977 to 1985, increasing thereafter until 2007. The increase from 2003 to 2007 was significant in organized sport but not in unorganized leisure time physical activity. It is concluded that there is an upward trend in Finnish adolescents' leisure time physical activity and in organized sport in particular, and that the increase in activity has been greater in girls than boys.
Motivation in physical education across the primary—secondary school transition
Authors: Warburton Victoria , Spray Christopher
Published: May 2008

The purpose of this study was to examine the temporal patterns of approach-avoidance achievement goals, implicit theories of ability and perceived competence in physical education across the transition from primary to secondary school. We also evaluated the predictive utility of implicit theories and perceived competence with regard to achievement goal adoption, and determined the moderating influence of gender on temporal patterns and antecedent—goal relationships. One hundred and forty pupils (mean age at start of study = 11.37 years, SD = .28) completed measures of entity and incremental beliefs, perceived competence and goals on four occasions during a 12-month period. Mastery-approach, performance-approach and performance-avoidance goals, as well as entity and incremental beliefs, exhibited a linear decline over time. Mastery-avoidance goals showed no significant change. Girls exhibited a linear decline in perceived competence, whereas for boys the trajectory was curvilinear. Competence perceptions predicted initial scores, but not rate of change, on mastery-approach and both types of performance goals. Incremental beliefs predicted rate of change in mastery-approach goal adoption, whereas entity beliefs were associated with changes in performance-avoidance goals and initial scores on performance-approach goals. Limited differences between boys and girls in these antecedent—goal relationships were observed.
Adolescent girls' perceptions of physical activity: A focus group study
Authors: Whitehead Sarah , Biddle Stuart
Published: May 2008

Low levels of physical activity among adolescent girls are a cause for concern. Examining girls' physical activity perceptions and motivations through in-depth qualitative research allows for greater understanding of the reasons behind their physical activity-related choices. Forty-seven girls aged 14 to 16 years participated in exploratory focus group discussions. Thematic analysis was carried out in which data were analysed inductively using a constant comparison method. The findings illustrate the extent to which adolescent girls' physical activity participation is affected by social influences and perceived societal norms. Furthermore, changing priorities throughout adolescence mean that physical activity is deprioritized, with many girls stating that they cannot be bothered to take part. Recommendations to increase participation include encouraging parental support, introducing peer mentoring schemes involving girls who enjoy and regularly participate in physical activity and providing activities for adolescent girls that are fun, informal in nature and involve participation with friends.
Articulating a Merleau-Pontian phenomenology of physical education: The quest for active student engagement and authentic assessment in high-stakes examination awards
Authors: Thorburn Malcolm
Published: May 2008

In an earlier paper some of the conceptual and curriculum coherence challenges of linking practically based experiential learning with authentic attainment in high-stakes examination awards in physical education were analysed (Thorburn, 2007). Problems often existed for students in deriving subject knowledge understanding from tasks where there was a lack of personalized engagement in learning. Due to weaknesses in previous cognitive attempts to adequately describe intentional activity, this paper argues in preliminary fashion that articulating a Merleau-Pontian phenomenology of physical education could improve the methodological basis for linking students' lived-body experiences with the acquisition of an increasingly detailed subject knowledge, provided that learning intentions are clearly identified and achievable. The situation in Higher Still Physical Education (HSPE) in Scotland is reviewed as one curriculum example where teachers could, despite current problems, more authentically deploy phenomenology-informed methodologies in order to improve the authenticity of students' learning experiences and assessment results.
Multiple Virginity and Other Contested Realities in Taipei's Foreign Club Culture
Authors: Moskowitz Marc L.
Published: May 2008

In this article I explore the constructed realms of thought in the club Laowai and other western-style nightclubs in Taipei, Taiwan. These contested realities revolve around notions of foreign and local, masculine and feminine. In examining Taiwanese women's portrayal of selves as chaste in the setting of a pick-up bar we can explore the complicated web of contradictory messages in which purity is constructed and the foreign is simultaneously exalted and despised. In exploring these issues I address Taiwanese women's sexuality in relation to the representational appeal of, and ambivalence towards, western men. This, in turn, ties in with contested fantasies within one social space. The resulting analysis suggests that to reduce club cultures to the singular, even in one club, is a conceptual error, for there are several overlapping realities in any given locale.
Skills, Performance, and Earnings in the Tournament Compensation Model
Authors: Shmanske Stephen
Published: May 2008

Previous research on professional golf has estimated reduced-form models in which earnings are a function of skills measured as year-long averages. Using individual, tournament-level data, this article makes three improvements. First, the use of tournament-level data removes measurement error in the skills by adjusting the data for tournament-level idiosyncrasies such as the effect of altitude on driving distance. Second, the collection of microdata allows one to examine variance and skewness of the skills distributions in addition to just the mean. And third, the article estimates a structural model in which golfers use their skills to perform well in competitions by shooting low scores at one level, while those score distributions underlie the tournament earnings of the golfers at the other level. Tighter estimates of the coefficients are resolved and the overall adjusted R2 improves from 0.36 to more than 0.90.
Critical Ethical Reasoning and Role-Play
Authors: Simkins David W. , Steinkuehler Constance
Published: May 2008

Role-playing games provide a particularly fruitful environment for the development of critical, ethical reasoning skills, a core component in developing a citizenry capable of fully participating in a cosmopolitan, democratic society. In this study, ethnographic interview participants recount particularly engaging ethical situations in their own game play. Through their responses, thematic trends develop that help us identify key elements in games that provide opportunities for the development of these crucial skills.
Role of VEGF-D and VEGFR-3 in developmental lymphangiogenesis, a chemicogenetic study in Xenopus tadpoles
Authors: Ny Annelii , Koch Marta , Vandevelde Wouter , Schneider Martin , Fischer Christian , Diez-Juan Antonio , Neven Elke , Geudens Ilse , Maity Sunit , Moons Lieve , Plaisance Stéphane , Lambrechts Diether , Carmeliet Peter , Dewerchin Mieke
Published: May 2008

The importance of the lymphangiogenic factor VEGF-D and its receptor VEGFR-3 in early lymphatic development remains largely unresolved. We therefore investigated their role in Xenopus laevis tadpoles, a small animal model allowing chemicogenetic dissection of developmental lymphangiogenesis. Single morpholino antisense oligo knockdown of xVEGF-D did not affect lymphatic commitment, but transiently impaired lymphatic endothelial cell (LEC) migration. Notably, combined knockdown of xVEGF-D with xVEGF-C at suboptimal morpholino concentrations resulted in more severe migration defects and lymphedema formation than the corresponding single knockdowns. Knockdown of VEGFR-3 or treatment with the VEGFR-3 inhibitor MAZ51 similarly impaired lymph vessel formation and function and caused pronounced edema. VEGFR-3 silencing by morpholino knockdown, MAZ51 treatment, or xVEGF-C/D double knockdown also resulted in dilation and dysfunction of the lymph heart. These findings document a critical role of VEGFR-3 in embryonic lymphatic development and function, and reveal a previously unrecognized modifier role of VEGF-D in the regulation of embryonic lymphangiogenesis in frog embryos.
Vascular dysfunction in a murine model of severe hemolysis
Authors: Frei Anne C. , Guo YiHe , Jones Deron W. , Pritchard Kirkwood A. , Fagan Karen A. , Hogg Neil , Wandersee Nancy J.
Published: May 2008

Spectrin is the backbone of the erythroid cytoskeleton; sph/sph mice have severe hereditary spherocytosis (HS) because of a mutation in the murine erythroid α-spectrin gene. sph/sph mice have a high incidence of thrombosis and infarction in multiple tissues, suggesting significant vascular dysfunction. In the current study, we provide evidence for both pulmonary and systemic vascular dysfunction in sph/sph mice. We found increased levels of soluble cell adhesion molecules in sph/sph mice, suggesting activation of the vascular endothelium. We hypothesized that plasma hemoglobin released by intravascular hemolysis initiates endothelial injury through nitric oxide (NO) scavenging and oxidative damage. Likewise, electron paramagnetic resonance spectroscopy showed that plasma hemoglobin is much greater in sph/sph mice. Moreover, plasma from sph/sph mice had significantly higher oxidative potential. Finally, xanthine oxidase, a potent superoxide generator, is decreased in subpopulations of liver hepatocytes and increased on liver endothelium in sph/sph mice. These results indicate that vasoregulation is abnormal, and NO-based vasoregulatory mechanisms particularly impaired, in sph/sph mice. Together, these data indicate that sph/sph mice with severe HS have increased plasma hemoglobin and NO scavenging capacity, likely contributing to aberrant vasoregulation and initiating oxidative damage.
Constitutive expression of IL-12Rβ2 on human multiple myeloma cells delineates a novel therapeutic target
Authors: Airoldi Irma , Cocco Claudia , Giuliani Nicola , Ferrarini Marina , Colla Simona , Ognio Emanuela , Taverniti Giuseppe , Di Carlo Emma , Cutrona Giovanna , Perfetti Vittorio , Rizzoli Vittorio , Ribatti Domenico , Pistoia Vito
Published: May 2008

The interleukin-12 (IL-12) receptor (R) B2 gene acts as tumor suppressor in human acute and chronic B-cell leukemias/lymphomas and IL-12rb2–deficient mice develop spontaneously localized plasmacytomas. With this background, we investigated the role of IL-12Rβ2 in multiple myeloma (MM) pathogenesis. Here we show the following: (1) IL-12Rβ2 was expressed in primary MM cells but down-regulated compared with normal polyclonal plasmablastic cells and plasma cells (PCs). IL-6 dampened IL-12Rβ2 expression on polyclonal plasmablastic cells and MM cells. (2) IL-12 reduced the proangiogenic activity of primary MM cells in vitro and decreased significantly (P = .001) the tumorigenicity of the NCI-H929 cell line in SCID/NOD mice by inhibiting cell proliferation and angiogenesis. The latter phenomenon was found to depend on abolished expression of a wide panel of proangiogenic genes and up-regulated expression of the antiangiogenic genes IFN-γ, IFN-α, platelet factor-4, and TIMP-2. Inhibition of the angiogenic potential of primary MM cells was related to down-regulated expression of the proangiogenic genes CCL11, vascular endothelial-cadherin, CD13, and AKT and to up-regulation of an IFN-γ–related antiangiogenic pathway. Thus, IL-12Rβ2 directly restrains MM cell growth, and targeting of IL-12 to tumor cells holds promise as new therapeutic strategy.
Inhibition of the TGF-β receptor I kinase promotes hematopoiesis in MDS
Authors: Zhou Li , Nguyen Aaron N. , Sohal Davendra , Ying Ma Jing , Pahanish Perry , Gundabolu Krishna , Hayman Josh , Chubak Adam , Mo Yongkai , Bhagat Tushar D. , Das Bhaskar , Kapoun Ann M. , Navas Tony A. , Parmar Simrit , Kambhampati Suman , Pellagatti Andrea , Braunchweig Ira , Zhang Ying , Wickrema Amittha , Medicherla Satyanarayana , Boultwood Jacqueline , Platanias Leonidas C. , Higgins Linda S. , List Alan F. , Bitzer Markus , Verma Amit
Published: May 2008

MDS is characterized by ineffective hematopoiesis that leads to peripheral cytopenias. Development of effective treatments has been impeded by limited insight into pathogenic pathways governing dysplastic growth of hematopoietic progenitors. We demonstrate that smad2, a downstream mediator of transforming growth factor–β (TGF-β) receptor I kinase (TBRI) activation, is constitutively activated in MDS bone marrow (BM) precursors and is overexpressed in gene expression profiles of MDS CD34+ cells, providing direct evidence of overactivation of TGF-β pathway in this disease. Suppression of the TGF-β signaling by lentiviral shRNA-mediated down-regulation of TBRI leads to in vitro enhancement of hematopoiesis in MDS progenitors. Pharmacologic inhibition of TBRI (alk5) kinase by a small molecule inhibitor, SD-208, inhibits smad2 activation in hematopoietic progenitors, suppresses TGF-β–mediated gene activation in BM stromal cells, and reverses TGF-β–mediated cell-cycle arrest in BM CD34+ cells. Furthermore, SD-208 treatment alleviates anemia and stimulates hematopoiesis in vivo in a novel murine model of bone marrow failure generated by constitutive hepatic expression of TGF-β1. Moreover, in vitro pharmacologic inhibition of TBRI kinase leads to enhancement of hematopoiesis in varied morphologic MDS subtypes. These data directly implicate TGF-β signaling in the pathobiology of ineffective hematopoiesis and identify TBRI as a potential therapeutic target in low-risk MDS.
Discovery and assembly of repeat family pseudomolecules from sparse genomic sequence data using the Assisted Automated Assembler of Repeat Families (AAARF) algorithm
Authors: DeBarry Jeremy D , Liu Renyi , Bennetzen Jeffrey L
Published: May 2008

Background

Higher eukaryotic genomes are typically large, complex and filled with both genes and multiple classes of repetitive DNA. The repetitive DNAs, primarily transposable elements, are a rapidly evolving genome component that can provide the raw material for novel selected functions and also indicate the mechanisms and history of genome evolution in any ancestral lineage. Despite their abundance, universality and significance, studies of genomic repeat content have been largely limited to analyses of the repeats in fully sequenced genomes.

Results

In order to facilitate a broader range of repeat analyses, the Assisted Automated Assembler of Repeat Families algorithm has been developed. This program, written in PERL and with numerous adjustable parameters, identifies sequence overlaps in small shotgun sequence datasets and walks them out to create long pseudomolecules representing the most abundant repeats in any genome. Testing of this program in maize indicated that it found and assembled all of the major repeats in one or more pseudomolecules, including coverage of the major Long Terminal Repeat retrotransposon families. Both Sanger sequence and 454 datasets were appropriate.

Conclusion

These results now indicate that hundreds of higher eukaryotic genomes can be efficiently characterized for the nature, abundance and evolution of their major repetitive DNA components.
Multilocus analysis of introgression between two sand fly vectors of leishmaniasis
Authors: Mazzoni Camila J , Araki Alejandra S , Ferreira Gabriel EM , Azevedo Renata VDM , Barbujani Guido , Peixoto Alexandre A
Published: May 2008

Background

The phlebotomine sand flies (Diptera:Psychodidae)Lutzomyia (Nyssomyia) intermediaLutz & Neiva 1912 andLutzomyia (Nyssomyia) whitmaniAntunes & Coutinho 1932 are two very closely related species and important vectors of American cutaneous leishmaniasis. Two single-locus studies have revealed evidence for introgression between the two species in both mitochondrial and nuclear genomes. These findings have prompted the development of a multilocus approach to investigate in more detail the genetic exchanges between the two species.

Results

We analyzed ten nuclear loci using the "isolation with migration" model implemented in the IM program, finding evidence for introgression fromL. intermediatowardsL. whitmaniin three loci. These results confirm that introgression is occurring between the two species and suggest variation in the effects of gene flow among the different regions of the genome.

Conclusion

The demonstration that these two vectors are not fully reproductively isolated might have important epidemiological consequences as these species could be exchanging genes controlling aspects of their vectorial capacity.
Comparative expression profiling in grape (Vitis vinifera) berries derived from frequency analysis of ESTs and MPSS signatures
Authors: Iandolino Alberto , Nobuta Kan , da Silva Francisco Goes , Cook Douglas R , Meyers Blake C
Published: May 2008

Background

Vitis vinifera (V. vinifera) is the primary grape species cultivated for wine production, with an industry valued annually in the billions of dollars worldwide. In order to sustain and increase grape production, it is necessary to understand the genetic makeup of grape species. Here we performed mRNA profiling using Massively Parallel Signature Sequencing (MPSS) and combined it with available Expressed Sequence Tag (EST) data. These tag-based technologies, which do not require a priori knowledge of genomic sequence, are well-suited for transcriptional profiling. The sequence depth of MPSS allowed us to capture and quantify almost all the transcripts at a specific stage in the development of the grape berry.

Results

The number and relative abundance of transcripts from stage II grape berries was defined using Massively Parallel Signature Sequencing (MPSS). A total of 2,635,293 17-base and 2,259,286 20-base signatures were obtained, representing at least 30,737 and 26,878 distinct sequences. The average normalized abundance per signature was ~49 TPM (Transcripts Per Million). Comparisons of the MPSS signatures with available Vitis species' ESTs and a unigene set demonstrated that 6,430 distinct contigs and 2,190 singletons have a perfect match to at least one MPSS signature. Among the matched sequences, ESTs were identified from tissues other than berries or from berries at different developmental stages. Additional MPSS signatures not matching to known grape ESTs can extend our knowledge of the V. vinifera transcriptome, particularly when these data are used to assist in annotation of whole genome sequences from Vitis vinifera.

Conclusion

The MPSS data presented here not only achieved a higher level of saturation than previous EST based analyses, but in doing so, expand the known set of transcripts of grape berries during the unique stage in development that immediately precedes the onset of ripening. The MPSS dataset also revealed evidence of antisense expression not previously reported in grapes but comparable to that reported in other plant species. Finally, we developed a novel web-based, public resource for utilization of the grape MPSS data [1].
Knockdown of TFIIS by RNA silencing inhibits cancer cell proliferation and induces apoptosis
Authors: Hubbard Kyle , Catalano Jennifer , Puri Raj K , Gnatt Averell
Published: May 2008

Background

A common element among cancer cells is the presence of improperly controlled transcription. In these cells, the degree of specific activation of some genes is abnormal, and altering the aberrant transcription may therefore directly target cancer. TFIIS is a transcription elongation factor, which directly binds the transcription motor, RNA Polymerase II and allows it to read through various transcription arrest sites. We report on RNA interference of TFIIS, a transcription elongation factor, and its affect on proliferation of cancer cells in culture.

Methods

RNA interference was performed by transfecting siRNA to specifically knock down TFIIS expression in MCF7, MCF10A, PL45 and A549 cells. Levels of TFIIS expression were determined by the Quantigene method, and relative protein levels of TFIIS, c-myc and p53 were determined by C-ELISA. Induction of apoptosis was determined by an enzymatic Caspase 3/7 assay, as well as a non-enzymatic assay detecting cytoplasmic mono- and oligonucleosomes. A gene array analysis was conducted for effects of TFIIS siRNA on MCF7 and MCF10A cell lines.

Results

Knockdown of TFIIS reduced cancer cell proliferation in breast, lung and pancreatic cancer cell lines. More specifically, TFIIS knockdown in the MCF7 breast cancer cell line induced cancer cell death and increased c-myc and p53 expression whereas TFIIS knockdown in the non-cancerous breast cell line MCF10A was less affected. Differential effects of TFIIS knockdown in MCF7 and MCF10A cells included the estrogenic, c-myc and p53 pathways, as observed by C-ELISA and gene array, and were likely involved in MCF7 cell-death.

Conclusion

Although transcription is a fundamental process, targeting select core transcription factors may provide for a new and potent avenue for cancer therapeutics. In the present study, knockdown of TFIIS inhibited cancer cell proliferation, suggesting that TFIIS could be studied as a potential cancer target within the transcription machinery.
Skp2 expression is associated with high risk and elevated Ki67 expression in gastrointestinal stromal tumours
Authors: Di Vizio Dolores , Demichelis Francesca , Simonetti Sara , Pettinato Guido , Terracciano Luigi , Tornillo Luigi , Freeman Michael R , Insabato Luigi
Published: May 2008

Background

Gastrointestinal stromal tumors (GIST) exhibit an unpredictable clinical course and can rapidly progress to lethality. Predictions about the biological behavior of GIST are based on a number of canonical clinical and pathologic parameters whose validity in distinguishing between a benign and a malignant tumour is still imperfect. The aim of our study was to investigate the role of morphologic parameters and expression of cells cycle regulators as prognosticators in GIST.

Methods

We performed an immunohistochemical analysis for Ki67, p27Kip1, Jab1, and Skp2, on a Tissue Microarray (TMA) containing 94 GIST. Expression of the above proteins was correlated to classically used prognosticators, as well as to risk groups. Clinical significance of histologic and immunohistochemical features were evaluated in 59 patients for whom follow-up information was available.

Results

Overexpression of Ki67 and Skp2, and p27Kip1loss directly correlated with the high risk group (p = 0.03 for Ki67 and Skp2, p = 0.05 for p27Kip1). Jab1 expression did not exhibit correlation with risk. In 59 cases provided with clinical follow-up, high cellularity, presence of necrosis, and Ki67 overexpression were predictive of a reduced overall survival in a univariate model. The same parameters, as well as mitotic rate, tumour size, and p27Kip1loss were indicative of a shortened relapse free survival interval. High cellularity, and high mitotic rate retained their prognostic significance by multivariate analysis.

Conclusion

Our data suggest that a number of histologic parameters in combination with immunohistochemical expression of cell cycle regulators can facilitate risk categorization and predict biologic behavior in GIST. Importantly this study demonstrates, for the first time, that Skp2 expression correlates with Ki67 expression and high risk in GIST.
A comparison between one- and two-fluoroscopic techniques in percutaneous vertebroplasty
Authors: Li Yen-Yao , Huang Tsung-Jen , Cheng Chin-Chang , Hsu Robert Wen-Wei
Published: May 2008

Background

Percutaneous vertebroplasty (PV) is generally performed under fluoroscopic guidance. Technically, single fluoroscope is considered sufficient for effectively monitoring PV. However, single fluoroscopic technique might be time-consuming in rotating the C-arm of the fluoroscope for either antero-posterior (AP) or lateral radiographic view, and causing delay in detecting cement leakage that can occur if the correct sight is not given. The aim of the current investigation was to compare the efficacy and safety of performing PV using one or two sets of fluoroscope.

Methods

This retrospective study enrolled 43 patients with painful osteoporotic vertebral fractures and they were treated with one-level PV. A single orthopaedic surgeon operated on all these patients. The patients were divided into two groups on the basis of the method of fluoroscopic control. In Group 1 (15 patients), PV was performed under the assistance of one fluoroscope. In Group 2 (28 patients), PV was performed under the control of two fluoroscopes. The mean follow-up was 19 months (range, 12 to 30).

Results

Neither symptomatic cement leakage nor postoperative infection was found in both groups. The mean operation time in Group 2 was shorter, 37.8 vs. 31.0 minutes for Groups 1 and 2, P = 0.03. The incidence of cement leakage for Groups 1 and 2 was 26.7% (4/15) vs. 14.3% (4/28), respectively, P = 0.19.

Conclusion

We found that the two-fluoroscopic technique can provide simultaneous, real-time AP and lateral radiographic views to monitor entry point and cement delivery for PV and therefore reduce the operation time. The two-fluoroscopic technique did not require a complex manpower organization and has been proved to be a safe and effective technique for PV.
Minocycline attenuates lipopolysaccharide (LPS)-induced neuroinflammation, sickness behavior, and anhedonia
Authors: Henry Christopher J , Huang Yan , Wynne Angela , Hanke Mark , Himler Justin , Bailey Michael T , Sheridan John F , Godbout Jonathan P
Published: May 2008

Background

Activation of the peripheral innate immune system stimulates the secretion of CNS cytokines that modulate the behavioral symptoms of sickness. Excessive production of cytokines by microglia, however, may cause long-lasting behavioral and cognitive complications. The purpose of this study was to determine if minocycline, an anti-inflammatory agent and purported microglial inhibitor, attenuates lipopolysaccharide (LPS)-induced neuroinflammation, sickness behavior, and anhedonia.

Methods

In the first set of experiments the effect of minocycline pretreatment on LPS-induced microglia activation was assessed in BV-2 microglia cell cultures. In the second study, adult (3–6 m) BALB/c mice received an intraperitoneal (i.p.) injection of vehicle or minocycline (50 mg/kg) for three consecutive days. On the third day, mice were also injected (i.p.) with saline orEscherichia coliLPS (0.33 mg/kg) and behavior (i.e., sickness and anhedonia) and markers of neuroinflammation (i.e., microglia activation and inflammatory cytokines) were determined. In the final study, adult and aged BALB/c mice were treated with the same minocycline and LPS injection regimen and markers of neuroinflammation were determined. All data were analyzed using Statistical Analysis Systems General Linear Model procedures and were subjected to one-, two-, or three-way ANOVA to determine significant main effects and interactions.

Results

Minocycline blocked LPS-stimulated inflammatory cytokine secretion in the BV-2 microglia-derived cell line and reduced LPS-induced Toll-like-receptor-2 (TLR2) surface expression on brain microglia. Moreover, minocycline facilitated the recovery from sickness behavior (i.e., anorexia, weight loss, and social withdrawal) and prevented anhedonia in adult mice challenged with LPS. Furthermore, the minocycline associated recovery from LPS-induced sickness behavior was paralleled by reduced mRNA levels of Interleukin (IL)-1β, IL-6, and indoleamine 2, 3 dioxygenase (IDO) in the cortex and hippocampus. Finally, in aged mice, where exaggerated neuroinflammation was elicited by LPS, minocycline pretreatment was still effective in markedly reducing mRNA levels of IL-1β, TLR2 and IDO in the hippocampus.

Conclusion

These data indicate that minocycline mitigates neuroinflammation in the adult and aged brain and modulates the cytokine-associated changes in motivation and behavior.
Human T-cell leukemia virus type 2 post-transcriptional control protein p28 is required for viral infectivity and persistence in vivo
Authors: Yamamoto Brenda , Li Min , Kesic Matthew , Younis Ihab , Lairmore Michael D , Green Patrick L
Published: May 2008

Background

Human T-cell leukemia virus (HTLV) type 1 and type 2 are related but distinct pathogenic complex retroviruses. HTLV-1 is associated with adult T-cell leukemia and a variety of immune-mediated disorders including the chronic neurological disease termed HTLV-1-associated myelopathy/tropical spastic paraparesis. In contrast, HTLV-2 displays distinct biological differences and is much less pathogenic, with only a few reported cases of leukemia and neurological disease associated with infection. In addition to the structural and enzymatic proteins, HTLV encodes regulatory (Tax and Rex) and accessory proteins. Tax and Rex positively regulate virus production and are critical for efficient viral replication and pathogenesis. Using an over-expression system approach, we recently reported that the accessory gene product of the HTLV-1 and HTLV-2 open reading frame (ORF) II (p30 and p28, respectively) acts as a negative regulator of both Tax and Rex by binding to and retaining their mRNA in the nucleus, leading to reduced protein expression and virion production. Further characterization revealed that p28 was distinct from p30 in that it was devoid of major transcriptional modulating activity, suggesting potentially divergent functions that may be responsible for the distinct pathobiologies of HTLV-1 and HTLV-2.

Results

In this study, we investigated the functional significance of p28 in HTLV-2 infection, proliferation, and immortaliztion of primary T-cells in culture, and viral survival in an infectious rabbit animal model. An HTLV-2 p28 knockout virus (HTLV-2Δp28) was generated and evaluated. Infectivity and immortalization capacity of HTLV-2Δp28 in vitro was indistinguishable from wild type HTLV-2. In contrast, we showed that viral replication was severely attenuated in rabbits inoculated with HTLV-2Δp28 and the mutant virus failed to establish persistent infection.

Conclusion

We provide direct evidence that p28 is dispensable for viral replication and cellular immortalization of primary T-lymphocytes in cell culture. However, our data indicate that p28 function is critical for viral survival in vivo. Our results are consistent with the hypothesis that p28 repression of Tax and Rex-mediated viral gene expression may facilitate survival of these cells by down-modulating overall viral gene expression.