bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential Regulation of Kiss1 Expression by Melatonin and Gonadal Hormones in Male and Female Syrian Hamsters
Authors: Ansel L. , Bolborea M. , Bentsen A.H. , Klosen P. , Mikkelsen J.D. , Simonneaux V.
Published: March 2010

In seasonal breeders, reproduction is synchronized to seasons by day length via the pineal hormone melatonin. Recently, we have demonstrated that Kiss1, a key activator of the reproductive function, is down-regulated in sexually inactive hamsters maintained in inhibitory short days (SDs). In rodents, Kiss1 is expressed in the anteroventral periventricular nucleus (AVPV) and in the arcuate nucleus (ARC). Because both the duration of the nocturnal peak of melatonin and circulating sex steroid levels vary with photoperiod, the aim of this study was to determine whether melatonin and sex steroids differentially regulate Kiss1 expression in the ARC and the AVPV. Kiss1 expression was examined by in situ hybridization in both male and female hamsters kept in various experimental conditions, and we observed that 1) SD exposure markedly reduced Kiss1 expression in the ARC and AVPV of male and female hamsters as compared to LD animals, 2) sex steroid treatment in SD-adapted male and female hamsters increased the number of Kiss1 neurons in the AVPV but decreased it in the ARC, 3) melatonin administration to LD-adapted hamsters decreased Kiss1 mRNA level in both the AVPV and the ARC in intact animals, whereas in castrated hamsters, melatonin rapidly inhibited Kiss1 expression in the ARC but not in the AVPV, and 4) pinealectomy of male or female SD-adapted hamsters increased the number of Kiss1 neurons in the ARC but not in the AVPV. In conclusion, our data demonstrate that Kiss1 expression in the Syrian hamster hypothalamus is down-regulated in SD via different mechanisms. In the ARC, melatonin inhibits Kiss1 via a direct effect on the hypothalamus, and this effect is probably sex steroid dependent, whereas in the AVPV, the decrease in Kiss1 expression appears to be secondary to the melatonin-driven reduction of sex steroid levels. Taken together, our data support the hypothesis that ARC Kiss1 neurons mediate melatonin effects on the gonadotropic axis of the Syrian hamster.
Nuclear Receptor Rev-Erb-α Circadian Gene Variants and Lithium Carbonate Prophylaxis in Bipolar Affective Disorder
Authors: Campos-de-Sousa Sara , Guindalini Camila , Tondo Leonardo , Munro Janet , Osborne Sarah , Floris Gianfranco , Pedrazzoli Mario , Tufik Sergio , Breen Gerome , Collier David
Published: March 2010

Rev-erb-α is one of the key components of the mammalian circadian mechanism; recently, it was also reported to be involved in the biological action of lithium. We investigated whether polymorphisms in the Rev-erb- α gene are associated with the long-term efficacy of lithium carbonate therapy in bipolar affective disorder. Seven single nucleotide polymorphisms (SNPs) were genotyped in a well-characterized sample of patients from Sardinia, Italy, who were followed prospectively for up to 27 years. Genotypic and allelic analysis did not show evidence for association between the polymorphisms and the different levels of lithium response. Further analyses grouping the different levels of response demonstrated that when the patients were separated into groups of nonresponders versus individuals who have had at least a minor or modest improvement in frequency of episodes or admissions, there was a significant increase in the frequency of the T allele in the nonresponder group ( p = 0.0008). Logistic regression analyses showed that patients carrying at least one copy of the T allele for the rs2314339 marker were shown to be approximately 3.5 times more likely to have no improvement or even a worsening of the illness (odds ratio [OR], 3.56; 95% confidence interval [CI], 1.18-10.76). The results of this study may help to identify potential biological markers that can serve to predict the response of bipolar affective disorder patients to treatment, improving treatment efficacy.
Influence of Magnetic Field and Hydrostatic Initial Stress on Wave Reflection from a Generalized Thermoelastic Solid Half-space
Authors: Abo-Dahab S.M. , Mohamed R.A.
Published: March 2010

Using a generalized thermoelastic solid half-space, we estimate the impact of magnetic field, initial pressure and hydrostatic initial stress on reflection of P and SV waves. We consider a Green Lindsay model and present the governing equations for an isotropic homogeneous generalized thermoelastic solid under a magnetic field and hydrostatic initial stress. Lame’s potentials are used in two dimensions that tend to separate the governing equations into three equations that are sought in harmonic travelling wave form. We introduce the equations of the velocity of the P wave, thermal wave and SV wave. The boundary conditions for mechanical and Maxwell’s stresses and thermal insulation are applied to determine the reflection coefficients for the P wave, thermal wave and SV wave. Some new aspects are obtained of the reflection coefficients and displayed graphically and new conclusions are presented. Finally, it is shown that, under some conditions, previous results are special cases of our results.
Comparison Between Two SMA Constitutive Models for Seismic Applications
Authors: Amarante Dos Santos F.P. , Cismaşiu C.
Published: March 2010

This paper analyses and compares the dynamic behavior of superelastic shape memory alloy (SMA) systems based on two different constitutive models. The first model, although being able to describe the response of the material to complex uniaxial loading histories, is temperature and rate independent. The second model couples the mechanical and kinetic laws of the material with a balance equation considering the thermal effects. After numerical validation and calibration, the behavior of these two models is tested in single degree of freedom dynamic systems, with SMAs acting as restoring elements. Different dynamic loads are considered, including artificially generated seismic actions, in a numerical model of a railway viaduct. Finally, it is shown that, in spite of its simplicity, the temperature- and rate-independent model produces a set of very satisfying results. This, together with its robustness and straightforward computational implementation, yields a very appealing numerical tool to simulate superelastic passive control applications.
The Growth and Disruption of a “Free Space”: Examining a Suburban Do It Yourself (DIY) Punk Scene
Authors: Culton Kenneth R. , Holtzman Ben
Published: March 2010

This article builds on the literature on “free spaces.” The authors address several under examined aspects of this concept through an exploration of the Long Island Do It Yourself (DIY) punk scene. The DIY scene can be understood as a prefigurative space where particular values were espoused and celebrated. The authors analyze how participants understood the free space as well as the specific values that came along with identifying themselves as scene members. When these ideals clashed with a different conception of what the punk scene was all about, the “freeness” of the space came into question. This article examines the debate that occurred when the free space was thoroughly disrupted because of the intention of a popular band in the scene to sign a record contract. The authors conclude that although the infrastructure of spaces in the punk scene was strong, this did not preempt the development of an ideological schism.
Living with HIV/AIDS and Use of Online Support Groups
Authors: Mo Phoenix K.H. , Coulson Neil S.
Published: March 2010

The present study explores the association between online support group use and health status, coping and social support among 640 individuals with HIV/AIDS. Results suggested that frequent users tended to be female, younger, single, and in a more advanced disease stage. After controlling for covariates, frequent users reported poorer health than non-users. In addition, both frequent and infrequent users scored higher in planning, active coping, instrumental support and emotional support coping from the brief COPE. No significant difference was found for social support. Our results suggest that online support groups may potentially offer some benefits for those living with HIV/AIDS.
An investigation of victimization and the clinical course of chronic fatigue syndrome
Authors: Johnson Susan K. , Schmaling Karen B. , Dmochowski Jacek , Bernstein David
Published: March 2010

Medically unexplained syndromes, including chronic fatigue syndrome (CFS), have been associated with victimization in childhood and adulthood. The purpose of this study was to examine the associations of victimization experiences in childhood and adulthood with functional status and illness severity in a sample of patients with CFS using longitudinal data. In the sample of 93 patients with CFS, childhood abuse and neglect had greater impact than adulthood victimization. Overall, victimization experiences in childhood demonstrated modest associations with clinical outcomes in CFS, although several victimization experiences were in the opposite direction of expectations. Victimization predicted worse outcomes, but not worsening outcomes over time.
The effects of clown intervention on worries and emotional responses in children undergoing surgery
Authors: Costa Fernandes Sara , Arriaga Patrícia
Published: March 2010

This study investigated whether clown intervention could reduce preoperative worries and the affective responses of children undergoing minor surgery. Parental anxiety was also tested. Child’s age, previous hospitalization, and temperament were tested as predictors of the child’s responses during this preoperative phase. Seventy children were assigned to one of two groups: children accompanied by their parents and a pair of clowns or, those accompanied by the parents but without the clowns. The results emphasized the relevance of clown intervention on the reduction of preoperative worries and emotional responses, not only in children but also in their parents.
Anti-fat, pro-slim, or both?
Authors: Roddy Sarah , Stewart Ian , Barnes-Holmes Dermot
Published: March 2010

Two measures of implicit attitudes, the Implicit Relational Assessment Procedure (IRAP) and the Implicit Association Test (IAT), were compared with each other and with a measure of explicit attitudes in the assessment of implicit pro-slim/anti-fat bias. Results from both implicit tests indicated higher levels of bias than revealed by the explicit measure. The IRAP data suggested that it was participants’ pro-slim rather than anti-fat bias, which was driving this effect. Explicit attitudes and feelings towards the overweight were significant predictors of behavioural intentions towards the overweight with the IRAP offering a greater contribution to predictive validity than the IAT.
A prospective investigation of interpersonal influences on the pursuit of muscularity in late adolescent boys and girls
Authors: Shomaker Lauren B. , Furman Wyndol
Published: March 2010

This project examined whether interpersonal pressure to be muscular predicted late adolescents’ pursuit of muscularity. Participants were 199 adolescents (16—19 years), mothers ( n = 175), and friends ( n = 159), assessed at two annual times. Pressure to be muscular was assessed with adolescents’, mothers’, and friends’ reports of their relationships. Adolescents reported pressure from fathers and romantic partners, appearance satisfaction, disordered eating, and pursuit of muscularity. Adolescents’, mothers’, and friends’ reports of pressure related to pursuit of muscularity at both times. Adolescents’ perceptions and mothers’ reports prospectively predicted pursuit of muscularity. Findings highlight the relevance of relationships to pursuit of muscularity in late adolescents.
Interdisciplinary physical activity counseling in primary care
Authors: O'Sullivan Tracey L. , Fortier Michelle S. , Faubert Christine , Culver Diane , Blanchard Chris , Reid Robert , Hogg William E.
Published: March 2010

The Physical Activity Counseling randomized controlled trial integrated a physical activity (PA) counselor into a primary care practice to provide intensive counseling to sedentary patients following brief counseling from their regular health care provider. This article presents the voices of 15 patients, who through a series of 3 interviews, described their experience with this 3-month combined provider PA counseling intervention. Patient satisfaction was a dominant emergent theme, and the patients were particularly positive about the quality of care and educational support for lifestyle change. They favored the tailored approach and felt the strategies for overcoming PA barriers were helpful.
Kidney Patients’ Intention to Receive a Deceased Donor Transplant
Authors: Waterman Amy D. , Robbins Mark L. , Paiva Andrea L. , Hyland Shelley S.
Published: March 2010

In order to sustain life, patients whose kidneys fail must receive dialysis or obtain a transplant. This study reports on the development and validation of measures of Stage of Change, Decisional Balance and Self-efficacy based on the Transtheoretical Model (TTM) to assess patients’ readiness to receive a deceased donor transplant. We surveyed 293 transplant-eligible kidney patients about their deceased donation readiness. Exploratory and confirmatory analyses for all measures demonstrated factor structures similar to previous application of the TTM to other health behaviors, excellent model fit and good internal and external validity. These brief, reliable instruments with good psychometric properties can guide the development of improved, individually-tailored transplant education for patients.
Obesity Treatment Tailored for a Catholic Faith Community
Authors: Krukowski Rebecca A. , Lueders Natalie K. , Prewitt T. Elaine , Williams D. Keith , Smith West Delia
Published: March 2010

Most faith-based obesity intervention research has been conducted in African-American Protestant churches. However, Catholic communities might also benefit from a faith-tailored approach. Overweight Catholic individuals ( n = 34, 71% female) were randomized to a Catholic-tailored or standard behavioral 16-week group weight control program. Both conditions experienced significant weight losses (Catholic-tailored: -8.1 + 4.1%, Standard: -7.9 + 4.2%); however, treatment satisfaction was significantly greater in the Catholic-tailored program. The Catholic-tailored program experienced trends for greater attendance, more completed self-monitoring journals, and smaller weight regain six months post-treatment than the standard program. Catholic-tailored programs may represent a feasible, culturally acceptable and effective approach to weight loss/maintenance in this faith community.
The Influence of Vaccine-critical Websites on Perceiving Vaccination Risks
Authors: Betsch Cornelia , Renkewitz Frank , Betsch Tilmann , Ulshöfer Corina
Published: March 2010

This large-scale Internet-experiment tests whether vaccine-critical pages raise perceptions of the riskiness of vaccinations and alter vaccination intentions. We manipulated the information environment (vaccine-critical website, control, both) and the focus of search (on vaccination risks, omission risks, no focus). Our analyses reveal that accessing vaccine-critical websites for five to 10 minutes increases the perception of risk of vaccinating and decreases the perception of risk of omitting vaccinations as well as the intentions to vaccinate. In line with the ‘risk-as-feelings’ approach, the affect elicited by the vaccine-critical websites was positively related to changes in risk perception.
Motives and Health-related Behaviours
Authors: Aspden Trefor , Ingledew David K. , Parkinson John A.
Published: March 2010

We investigated the phenomena of equipotentiality (one dispositional motive expressed through more than one behaviour) and equifinality (one behaviour serving more than one motive). In a cross-sectional survey, 244 young adults completed measures of sun-related behaviour and risky sexual behaviour, participatory motives for the behaviours and life goals (representing dispositional motives). Equipotentiality was demonstrated, in that power and diversity life goals each predicted more than one behaviour. Equifinality was demonstrated, in that sun exposure and risky sexual behaviour were each predicted by more than one life goal. Participatory motives mediated these relationships. Equipotentiality and equifinality need to be taken into account in health promotion.
Indigenous traces in colonial spaces
Authors: Silliman Stephen
Published: March 2010

This article reconsiders how archaeologists find Indigenous people, particularly Native Americans, in past colonial communities. Significant progress has been made in studying indigenous living areas associated with colonial communities but not in recovering evidence for (or even remembering) Native people laboring in distinctly colonial spaces. I propose that the reason for the lag lies in an incomplete perspective on material culture and space that denies their polyvalent and ambiguous, yet informative and manifestly real, nature. A new perspective can be forged with greater use of social theory pertaining to practice, space, and labor. Reconceptualizing material culture and space in colonial contexts requires that archaeologists acknowledge the role of labor relations in structuring material and spatial practices and not conflate origins of artifacts and spaces with other possible social meanings derived from practice. This article examines these two dimensions with three North American cases from New England, Florida, and California.
Death and the family
Authors: Sayer Duncan
Published: March 2010

Who buried the dead? Cemeteries contain the graves of people from local communities but the individual dead were buried by only a few members of that community, those that survived them. This article seeks to use detailed chronological information to analyse funerary data and proposes a system for establishing a generation-based dating scheme. Such a scheme advances studies of archaeological cemeteries by the discussion of life-time rather than end-of-life chronologies. This will enhance studies of social relationships, memory and the transmission of specific social identities by moving towards a more experiential archaeology. Specifically, I use a detailed study of three Anglo-Saxon cemeteries to investigate notions of social time. This article uses generational information in conjunction with other mortuary differentiations such as spatial location, age, life course, gender and grave-good wealth to show that Anglo-Saxon social status was determined by who was alive at any one time, and that the status of head of the household was not entirely determined by gender, but by who was able to fill the role.
Taupita
Authors: Connaughton Sean P. , Taché Karine , Burley David V.
Published: March 2010

Recent excavations at the archaeological site of Nukuleka on Tongatapu in the Tongan Archipelago have yielded the largest Lapita collection of perforated Ark ( Anadara) shells known to date. In this article, we focus on the unusually large collection of modified Ark shells from Nukuleka in an attempt to unravel the ambiguity that surrounds their functional interpretation. Former interpretations of perforated Anadara as shell net weights may only explain one possible cause of their construction. We proffer, through relational analogy, that we are witnessing a 3000-year-old Lapita shell game.
International students’ experiences and attitudes at a US host institution: Self-reports and future recommendations
Authors: Lee Jenny J.
Published: March 2010

This article examines international students’ experiences at a US university and how these might influence them to recommend or not recommend that others from their home country attend it. Data were collected via online survey at a large public university in the US Southwest. Students from predominantly non-White regions of origin had more negative experiences. Findings suggest that perceptions of unequal treatment are a major factor influencing international students’ attitudes.
The International Baccalaureate Diploma and student attitudes: An exploratory study
Authors: Wilkinson Veronica , Hayden Mary
Published: March 2010

This article presents a summary of the findings of a recent study that points to the importance of informal, out of classroom, interactions in effecting change in student attitudes as they pass through the two-year International Baccalaureate Diploma Programme, designed as an internationally recognized pre-university programme for students worldwide. Possible reasons for the changes in attitudes that were found, and the major factors that students claimed were responsible, are discussed.
Sequential meta-analysis: an efficient decision-making tool
Authors: van der Tweel Ingeborg , Bollen Casper
Published: March 2010

Background A cumulative meta-analysis of successive randomized controlled trials (RCTs) can be used to decide whether enough evidence has been obtained comparing a control and an intervention treatment or whether a new RCT should be initiated. In general, no adjustment is made for repeatedly testing the null hypothesis of treatment equivalence on cumulative data. Neither can the power of the statistical test be quantified. Recently, trial sequential analysis (TSA) was suggested to ‘. . . establish when firm evidence is reached in cumulative meta-analysis’. TSA is based on α-spending functions and necessitates a prior estimate of the total information size. Various information sizes were suggested.

Purpose The aim of this study is to compare TSA with sequential meta-analysis (SMA) following Whitehead’s boundaries approach.

Methods We compare TSA and SMA by re-analysis of a number of published examples.

Results Re-analysis of the examples shows that for an SMA: (1) no prior estimate for total information size is necessary and thus one set of boundaries suffices; (2) stopping a cumulative meta-analysis for futility is an option; (3) the power can be quantified; (4) point and interval estimates are adjusted for the multiple testing; and (5) gains in efficiency can be achieved, both for efficacy and for futility and thus ethical and economical benefits can be obtained.

Limitations Estimates for between-trial variability are unstable for a small number of trials. The behavior of a newly proposed estimate should be subject of further investigation.

Conclusion SMA is a useful tool to investigate the cumulative evidence from successive RCTs.
A Bayesian dose-finding trial with adaptive dose expansion to flexibly assess efficacy and safety of an investigational drug
Authors: Berry Scott M , Spinelli Walter , Littman Gary S , Liang John Z , Fardipour Parvin , Berry Donald A , Lewis Roger J , Krams Michael
Published: March 2010

Background Adaptive dose-ranging trials are more efficient than traditional approaches and may be designed to explicitly address the goals and decisions inherent in learn-phase drug development. We report the design, implementation, and outcome of an innovative Bayesian, response-adaptive, dose-ranging trial of an investigational drug in patients with diabetes, incorporating a dose expansion approach to flexibly address both efficacy and safety.

Purpose The design was developed to assess whether one or more doses of an investigational drug demonstrated superior efficacy to an active control while maintaining an acceptable safety profile.

Methods The trial used a two-stage design, in which patients were initially allocated equally to placebo, investigational drug at a low and a medium dose, and an active control. Movement to the second stage was contingent upon evidence of efficacy (measured by change in fasting blood glucose) to add a very low dose of the investigational drug and of safety (measured by weight gain) to add a high dose of the investigational drug. The design incorporated a longitudinal model to maximize use of incomplete data, predictive probabilities to guide the decisions to terminate the trial for futility or move on to Stage 2, and a dose-response model in Stage 2 to borrow information across adjacent doses. Extensive simulations were used to fine tune trial parameters, to define operating characteristics, and to determine the required sample sizes. A data monitoring committee was provided with frequent reports to aid in trial oversight.

Results In Stage 1, as trial data accrued, the predictive probability that either the low or medium dose of the investigational drug was superior to the active control fell to low values. Stage 1 termination was recommended after 199 subjects were randomized, out of a maximum trial size of 500 subjects, and the final sample size was 218. Thus the trial did not progress to Stage 2.

Limitations Because of the relatively narrow dose range to be assessed, and the inability to utilize the highest dose at the beginning of the trial, a fully responsive-adaptive design incorporating dose-response modeling was not considered a viable option. This limited the efficiency gains possible with a full set of adaptive design elements.

Conclusions The two-stage dose-expansion design functioned as designed, recommending early termination based on a low probability that the tested doses had efficacy greater than the active control. Clinical Trials 2010; 7: 121—135. http://ctj.sagepub.com
Does treatment effect depend on control event rate? Revisiting a meta-analysis of suicidality and antidepressant use in children
Authors: Proschan Michael A , Brittain Erica H , Fay Michael P
Published: March 2010

Background Weisberg et al. (Clin Trials 2009, 6: 109—18) illustrate that entry criteria in randomized trials can lead to results that are biased for the target population. Presenting data from a previously published meta-analysis of the effect of antidepressants in children on suicidality, they suggest a relationship between the control event rate and relative risk.

Purpose Our purpose is threefold: (1) to show that natural methods of demonstrating a relationship between the control event rate and relative treatment benefit are fraught with danger, (2) to develop better methods, and (3) to assess whether there is evidence of such a relationship in the suicidality meta-analysis. Methods We propose an improved graphical method and an exact and approximate test of whether the treatment effect increases (or decreases) with the control event rate.

Results The apparent relationship in the naive plot of relative risk against control rate is actually no stronger than what would be expected by chance. Results of our test do not support the conclusion that the odds ratio for suicidality varies with the control rate (one-sided p = 0.39).

Limitations We are not able to apply the exact test to this data set. Simulation results indicate that the relationship would have to be very strong to detect it with these sample sizes and control event rates.

Conclusions The difficulty in showing that the treatment effect in clinical trials differs by control rate is caused by 3 factors: (1) artificial correlation between a relative risk and control rate, (2) regression dilution bias because the independent variable — the control proportion — is subject to random variability, and (3) low power because we are trying to detect an interaction. Our graph and test are useful tools. Using them, we found no support for a relationship between the control event rate and treatment effect on suicidality. Clinical Trials 2010; 7: 109—117. http://ctj.sagepub.com
Clinical trials for predictive medicine: new challenges and paradigms
Authors: Simon Richard
Published: March 2010

Background Developments in biotechnology and genomics have increased the focus of biostatisticians on prediction problems. This has led to many exciting developments for predictive modeling where the number of variables is larger than the number of cases. Heterogeneity of human diseases and new technology for characterizing them presents new opportunities and challenges for the design and analysis of clinical trials.

Purpose In oncology, treatment of broad populations with regimens that do not benefit most patients is less economically sustainable with expensive molecularly targeted therapeutics. The established molecular heterogeneity of human diseases requires the development of new paradigms for the design and analysis of randomized clinical trials as a reliable basis for predictive medicine [Simon R. An agenda for clinical trials: clinical trials in the genomic era. Clin Trials 2004; 1:468—70, Simon R. New challenges for 21st century clinical trials. Clin Trials 2007; 4: 167—9.]. Results We have reviewed prospective designs for the development of new therapeutics with candidate predictive biomarkers. We have also outlined a prediction based approach to the analysis of randomized clinical trials that both preserves the type I error and provides a reliable internally validated basis for predicting which patients are most likely or unlikely to benefit from the new regimen. Conclusions Developing new treatments with predictive biomarkers for identifying the patients who are most likely or least likely to benefit makes drug development more complex. But for many new oncology drugs it is the only science based approach and should increase the chance of success. It may also lead to more consistency in results among trials and has obvious benefits for reducing the number of patients who ultimately receive expensive drugs which expose them risks of adverse events but no benefit. This approach also has great potential value for controlling societal expenditures on health care. Development of treatments with predictive biomarkers requires major changes in the standard paradigms for the design and analysis of clinical trials. Some of the key assumptions upon which current methods are based are no longer valid. In addition to reviewing a variety of new clinical trial designs for co-development of treatments and predictive biomarkers, we have outlined a prediction based approach to the analysis of randomized clinical trials. This is a very structured approach whose use requires careful prospective planning. It requires further development but may serve as a basis for a new generation of predictive clinical trials which provide the kinds of reliable individualized information which physicians and patients have long sought, but which have not been available from the past use of post-hoc subset analysis. Clinical Trials 2010; 7: 516—524. http://ctj.sagepub.com
Rallying Around the Flag
Authors: Sosale Sujatha
Published: March 2010

/ This study employs Anderson’s thesis of the imagined community as a heuristic to explain the formation of a national media sphere in the journalistic domain. Based on the argument that nationalistic sentiment continues to serve as an identity anchor in the contemporary global era during times of crisis, this study maps the emergence of a national ‘mediascape’ in The New York Times’s coverage of media industries following the historic plane crashes of 11 September 2001 in the US. The properties of an imagined community as delineated by Anderson — boundaries (limits), sovereignty (autonomy) and community (ideological proximity) — constituted the primary categories of analysis for examining the peak coverage of media industries in the three months following the crisis. The analyses demonstrate the mechanisms in the coverage through which a national mediascape was constructed at this time, drawing global media within the national fold.
Limits of National Discourse on a Transnational Phenomenon
Authors: Polson Erika , Kahle Shannon
Published: March 2010

/ Although global migration is a complex transnational issue, media and policy discussions in wealthy regions often isolate immigration discourse within national frameworks. Using a Special Report on the BBC Online as a case study (and a ‘best case’ example of immigration reporting), this article illustrates the problems that are masked by ‘objective’ language used within the realm of national identity, and calls for media and policy researchers dealing with immigration to take a transnational view of societal transformations related to migration. In conducting a qualitative analysis that tests media frames against an established goal, this case study suggests the value of adding a normative aspect to framing research.
Toll-like receptor 9 signaling by CpG-B oligodeoxynucleotides induces an apoptotic pathway in human chronic lymphocytic leukemia B cells
Authors: Liang Xueqing , Moseman E. Ashley , Farrar Michael A. , Bachanova Veronika , Weisdorf Daniel J. , Blazar Bruce R. , Chen Wei
Published: March 2010

Chronic lymphocytic leukemia (CLL) is the most prevalent human leukemia and is characterized by the progressive accumulation of long-lived malignant B cells. Here we show that human B-CLL cells selectively express high levels of Toll-like receptor 9 (TLR9) mRNA and proteins. Treating B-CLL cells with TLR9 agonists, type B CpG oligodeoxynucleotides (CpG-B ODNs), induces significant morphologic and phenotypic activation, altered cytokine production, reversal of signal transducer, and activator of transcription 1 (STAT1) phosphorylation state, followed by profound apoptosis of B-CLL cells that is CpG-B ODN treatment time- and dose-dependent. TLR9-CpG ODN ligation-induced apoptosis of B-CLL cells is confirmed by viable cell counts, annexin V/propidium iodide and tetramethyl-rhodamine ethylester staining, Western blots of the activation, and cleaved caspases and poly (ADP-ribose) polymerase. Triggering TLR9 by CpG-B ODN leads to nuclear factor-κB-dependent production of autocrine interleukin-10, which activates JAK/STAT pathway-dependent tyrosine phosphorylation of STAT1 proteins and thereby provokes an apoptosis pathway in B-CLL cells. Treating B-CLL cells in vitro or in vivo with CpG-B ODN reduces the number of leukemia cells that engraft in NOD-scid mice. These findings provide new understanding of CpG ODN-mediated antitumor effects and support for the development of TLR9-targeted therapy for human CLL.
Down-regulation of GATA1 uncouples STAT5-induced erythroid differentiation from stem/progenitor cell proliferation
Authors: Wierenga Albertus T. J. , Vellenga Edo , Schuringa Jan Jacob
Published: March 2010

Previously, we have shown that overexpression of an activated mutant of signal transducer and activator of transcription-5 (STAT5) induces erythropoiesis, impaired myelopoiesis, and an increase in long-term proliferation of human hematopoietic stem/progenitor cells. Because GATA1 is a key transcription factor involved in erythropoiesis, the involvement of GATA1 in STAT5-induced phenotypes was studied by shRNA-mediated knockdown of GATA1. CD34+ cord blood cells were double transduced with a conditionally active STAT5 mutant and a lentiviral vector expressing a short hairpin against GATA1. Erythropoiesis was completely abolished in the absence of GATA1, indicating that STAT5-induced erythropoiesis is GATA1-dependent. Furthermore, the impaired myelopoiesis in STAT5-transduced cells was restored by GATA1 knockdown. Interestingly, early cobblestone formation was only modestly affected, and long-term growth of STAT5-positive cells was increased in the absence of GATA1, whereby high progenitor numbers were maintained. Thus, GATA1 down-regulation allowed the dissection of STAT5-induced differentiation phenotypes from the effects on long-term expansion of stem/progenitor cells. Gene expression profiling allowed the identification of GATA1-dependent and GATA1-independent STAT5 target genes, and these studies revealed that several proliferation-related genes were up-regulated by STAT5 independent of GATA1, whereas several erythroid differentiation-related genes were found to be GATA1 as well as STAT5 dependent.
Genome-wide copy number analysis of Hodgkin Reed-Sternberg cells identifies recurrent imbalances with correlations to treatment outcome
Authors: Steidl Christian , Telenius Adele , Shah Sohrab P. , Farinha Pedro , Barclay Lorena , Boyle Merrill , Connors Joseph M. , Horsman Douglas E. , Gascoyne Randy D.
Published: March 2010

In classical Hodgkin lymphoma (cHL) the mechanisms underlying primary refractory disease and relapse remain unknown. To gain further insight into cHL pathogenesis and genomic changes linked to treatment response, we studied 53 cHL patients by array comparative genomic hybridization, including 23 patients whose primary treatment failed, using DNA from microdissected HRS cells. Copy number alterations found in more than 20% of cases included gains of 2p, 9p, 16p, 17q, 19q, 20q, and losses of 6q, 11q, and 13q. We identified at high resolution recurrent changes defining minimally gained and lost regions harboring genes involved in nuclear factor κB signaling, such as REL, IKBKB, CD40, and MAP3K14. Gains of chromosome 16p11.2-13.3 were significantly more frequent in pretreatment and relapse biopsies of unresponsive patients and were associated with shortened disease-specific survival (P = .028). In the therapy-resistant HL cell line KMH2, we found genomic gains and overexpression of the multidrug resistance gene ABCC1 mapping to cytoband 16p13.11. We show that doxorubicin exposure to KMH2 induces ABCC1 expression and that siRNA silencing of ABCC1 sensitizes KMH2 cells to doxorubicin toxicity in vitro, suggesting that overexpression of ABCC1 contributes to the drug resistance phenotype found in KMH2.
CD16− natural killer cells: enrichment in mucosal and secondary lymphoid tissues and altered function during chronic SIV infection
Authors: Reeves R. Keith , Gillis Jacqueline , Wong Fay E. , Yu Yi , Connole Michelle , Johnson R. Paul
Published: March 2010

Natural killer (NK) cells contribute to control of HIV/SIV infection. We defined macaque NK-cell subsets based on expression of CD56 and CD16 and found their distribution to be highly disparate. CD16+ NK cells predominated in peripheral blood, whereas most mucosal NK cells were CD56+, and lymph nodes contained both CD56+ and CD16−CD56− (double-negative [DN]) subsets. Functional profiles were also distinct among subsets—CD16+ NK cells expressed high levels of cytolytic molecules, and CD56+ NK cells were predominantly cytokine-secreting cells, whereas DN NK possessed both functions. In macaques chronically infected with SIV, circulating CD16+ and DN NK cells were expanded in number and, although markers of cytoxicity increased, cytokine secretion decreased. Notably, CD56+ NK cells in SIV-infected animals up-regulated perforin, granzyme B, and CD107a. In contrast, the lymph node–homing molecules CD62 ligand (CD62L) and C-C chemokine receptor type 7 (CCR7), which are expressed primarily on CD56+ and DN NK cells, were significantly down-regulated on NK cells from infected animals. These data demonstrate that SIV infection drives a shift in NK-cell function characterized by decreased cytokine production, expanded cytotoxicity, and trafficking away from secondary lymphoid organs, suggesting that the NK-cell repertoire is not only heterogeneous but also plastic.
Genomic analysis of expressed sequence tags in American black bear Ursus americanus
Authors: Zhao Sen , Shao Chunxuan , Goropashnaya Anna V , Stewart Nathan C , Xu Yichi , Tøien Øivind , Barnes Brian M , Fedorov Vadim B , Yan Jun
Published: March 2010

Background

Species of the bear family (Ursidae) are important organisms for research in molecular evolution, comparative physiology and conservation biology, but relatively little genetic sequence information is available for this group. Here we report the development and analyses of the first large scale Expressed Sequence Tag (EST) resource for the American black bear (Ursus americanus).

Results

Comprehensive analyses of molecular functions, alternative splicing, and tissue-specific expression of 38,757 black bear EST sequences were conducted using the dog genome as a reference. We identified 18 genes, involved in functions such as lipid catabolism, cell cycle, and vesicle-mediated transport, that are showing rapid evolution in the bear lineage Three genes, Phospholamban (PLN), cysteine glycine-rich protein 3 (CSRP3) and Troponin I type 3 (TNNI3), are related to heart contraction, and defects in these genes in humans lead to heart disease. Two genes, biphenyl hydrolase-like (BPHL) and CSRP3, contain positively selected sites in bear. Global analysis of evolution rates of hibernation-related genes in bear showed that they are largely conserved and slowly evolving genes, rather than novel and fast-evolving genes.

Conclusion

We provide a genomic resource for an important mammalian organism and our study sheds new light on the possible functions and evolution of bear genes.
Detection of novel 3' untranslated region extensions with 3' expression microarrays
Authors: Thorrez Lieven , Tranchevent Leon-Charles , Chang Hui Ju , Moreau Yves , Schuit Frans
Published: March 2010

Background

The 3' untranslated regions (UTRs) of transcripts are not well characterized for many genes and often extend beyond the annotated regions. Since Affymetrix 3' expression arrays were designed based on expressed sequence tags, many probesets map to intergenic regions downstream of genes. We used expression information from these probesets to predict transcript extension beyond currently known boundaries.

Results

Based on our dataset encompassing expression in 22 different murine tissues, we identified 845 genes with predicted 3'UTR extensions. These extensions have a similar conservation as known 3'UTRs, which is distinctly higher than intergenic regions. We verified 8 of the predictions by PCR and found all of the predicted regions to be expressed. The method can be extended to other 3' expression microarray platforms as we demonstrate with human data. Additional confirming evidence was obtained from public paired end read data.

Conclusions

We show that many genes have 3'UTR regions extending beyond currently known gene regions and provide a method to identify such regions based on microarray expression data. Since 3' UTR contain microRNA binding sites and other stability determining regions, identification of the full length 3' UTR is important to elucidate posttranscriptional regulation.
The ancient mammalian KRAB zinc finger gene cluster on human chromosome 8q24.3 illustrates principles of C2H2 zinc finger evolution associated with unique expression profiles in human tissues
Authors: Lorenz Peter , Dietmann Sabine , Wilhelm Thomas , Koczan Dirk , Autran Sandra , Gad Sophie , Wen Gaiping , Ding Guohui , Li Yixue , Rousseau-Merck Marie-Françoise , Thiesen Hans-Juergen
Published: March 2010

Background

Expansion of multi-C2H2 domain zinc finger (ZNF) genes, including the Krüppel-associated box (KRAB) subfamily, paralleled the evolution of tetrapodes, particularly in mammalian lineages. Advances in their cataloging and characterization suggest that the functions of the KRAB-ZNF gene family contributed to mammalian speciation.

Results

Here, we characterized the human 8q24.3 ZNF cluster on the genomic, the phylogenetic, the structural and the transcriptome level. Six (ZNF7, ZNF34, ZNF250, ZNF251, ZNF252, ZNF517) of the seven locus members contain exons encoding KRAB domains, one (ZNF16) does not. They form a paralog group in which the encoded KRAB and ZNF protein domains generally share more similarities with each other than with other members of the human ZNF superfamily. The closest relatives with respect to their DNA-binding domain were ZNF7 and ZNF251. The analysis of orthologs in therian mammalian species revealed strong conservation and purifying selection of the KRAB-A and zinc finger domains. These findings underscore structural/functional constraints during evolution. Gene losses in the murine lineage (ZNF16, ZNF34, ZNF252, ZNF517) and potential protein truncations in primates (ZNF252) illustrate ongoing speciation processes. Tissue expression profiling by quantitative real-time PCR showed similar but distinct patterns for all tested ZNF genes with the most prominent expression in fetal brain. Based on accompanying expression signatures in twenty-six other human tissues ZNF34 and ZNF250 revealed the closest expression profiles. Together, the 8q24.3 ZNF genes can be assigned to a cerebellum, a testis or a prostate/thyroid subgroup. These results are consistent with potential functions of the ZNF genes in morphogenesis and differentiation. Promoter regions of the seven 8q24.3 ZNF genes display common characteristics like missing TATA-box, CpG island-association and transcription factor binding site (TFBS) modules. Common TFBS modules partly explain the observed expression pattern similarities.

Conclusions

The ZNF genes at human 8q24.3 form a relatively old mammalian paralog group conserved in eutherian mammals for at least 130 million years. The members persisted after initial duplications by undergoing subfunctionalizations in their expression patterns and target site recognition. KRAB-ZNF mediated repression of transcription might have shaped organogenesis in mammalian ontogeny.
Neural computation of visual imaging based on Kronecker product in the primary visual cortex
Authors: Songnian Zhao , Qi Zou , Zhen Jin , Guozheng Yao , Li Yao
Published: March 2010

Background

What kind of neural computation is actually performed by the primary visual cortex and how is this represented mathematically at the system level? It is an important problem in the visual information processing, but has not been well answered. In this paper, according to our understanding of retinal organization and parallel multi-channel topographical mapping between retina and primary visual cortex V1, we divide an image into orthogonal and orderly array of image primitives (or patches), in which each patch will evoke activities of simple cells in V1. From viewpoint of information processing, this activated process, essentially, involves optimal detection and optimal matching of receptive fields of simple cells with features contained in image patches. For the reconstruction of the visual image in the visual cortex V1 based on the principle of minimum mean squares error, it is natural to use the inner product expression in neural computation, which then is transformed into matrix form.

Results

The inner product is carried out by using Kronecker product between patches and function architecture (or functional column) in localized and oriented neural computing. Compared with Fourier Transform, the mathematical description of Kronecker product is simple and intuitive, so is the algorithm more suitable for neural computation of visual cortex V1. Results of computer simulation based on two-dimensional Gabor pyramid wavelets show that the theoretical analysis and the proposed model are reasonable.

Conclusions

Our results are:

1. The neural computation of the retinal image in cortex V1 can be expressed to Kronecker product operation and its matrix form, this algorithm is implemented by the inner operation between retinal image primitives and primary visual cortex's column. It has simple, efficient and robust features, which is, therefore, such a neural algorithm, which can be completed by biological vision.

2. It is more suitable that the function of cortical column in cortex V1 is considered as the basic unit of visual image processing (such unit can implement basic multiplication of visual primitives, such as contour, line, and edge), rather than a set of tiled array filter. Fourier Transformation is replaced with Kronecker product, which greatly reduces the computational complexity. The neurobiological basis of this idea is that a visual image can be represented as a linear combination of orderly orthogonal primitive image containing some local feature. In the visual pathway, the image patches are topographically mapped onto cortex V1 through parallel multi-channels and then are processed independently by functional columns. Clearly, the above new perspective has some reference significance to exploring the neural mechanisms on the human visual information processing.